Horizon (1964–…): Season 48, Episode 15 - Defeating Cancer - full transcript
There is one disease that touches
all of our lives.
A disease whose diagnosis can be
devastating.
One of the hardest things was
actually telling the family,
especially our three children.
More than one in three of us
will get it in our lifetime.
Nobody knows if it's going to be
the last Christmas,
the last birthday, the last holiday,
and it's just that uncertainty.
Cancer is one of the most complex
diseases to treat,
because it's a part of us.
Cancer isn't an alien invasion
from outside,
it's actually part of the price
we pay for being human.
This programme follows three people
through
one of the most difficult times
of their lives.
I'm just repeating history now.
Dad died of it
and it looks like I'm going to.
Horizon has been given unprecedented
access behind the doors
of the Royal Marsden Hospital
in London,
where they are pioneering
some ground-breaking new treatments.
This is new to us, we've not done it
before, we've not given
this kind of dose,
with this technology.
On the day,
it will be nerve-wracking.
For Ray, Phil and Rosemary,
these treatments offer new hope.
And for all of us,
they hold the possibility that we
could one day defeat cancer.
It's summer 2011.
And Ray Dean is about to face
the biggest challenge of his life.
I used to be a professional
footballer,
played against some of
the best footballers in the country.
The most famous being Georgie,
Georgie Best.
And, er, yeah, played at Liverpool.
On the famous turf at Anfield,
in the cup match, yeah.
That was in the, erm,
in the younger days.
Seven years ago, Ray was diagnosed
with prostate cancer
and underwent an intensive
period of radiotherapy treatment.
It was seven weeks, five days a week,
I had 35 sessions.
So I started at about five o'clock in
the morning so that I could do
a bit of work, earn a bit of money,
and then go up there for
the treatment.
His treatment held the cancer at bay
for nearly five years.
But then Ray received the news
he'd been dreading -
the cancer had returned.
You get more and more confident
as the years go by that it's not
going to come back, but,
unfortunately, it has come back.
This time, Ray's options
for treatment are limited.
Now, his best hope lies with radical
developments in cancer medicine.
Hopefully, everything's going
to be all right.
I don't think the nerves will kick
in, I'm too old to have nerves now!
So, erm, yes.
It's just the build-up.
This robot could offer Ray
some hope.
It's part of a new generation
of advanced radiotherapy machines,
one of only a handful of its type
in the UK.
In charge of getting it
up and running is Dr Nick Van As.
Radiation remains the most effective
way of killing a cancer cell.
We could kill all cancer cells if
we could give them enough radiation,
the problem is we'd have to spare
the normal tissue around it.
So, the challenge is to get the
high dose of radiation to a cancer
and minimise the dose to
those surrounding tissues.
The robot is the newest arrival at
the Royal Marsden Hospital in
London.
Together with
its scientific partner,
the Institute of Cancer Research,
the hospital pioneers and
researches cutting-edge treatments.
It's nice to be working in a place
where we have the ability to invest
in new techniques and be, hopefully,
at the forefront of
developing where treatments
are going to be in ten years' time.
This robot is the hospital's latest
way of using radiation to kill
cancer cells.
It targets the cancer with
pin-point accuracy,
even as a patient moves
and breathes.
On the ceiling you can see that
there's two X-ray units,
one on each side, that's
for visualising the tumour, and then
that allows the robot to correct for
movement of the tumour in real time.
And then this over here is
a light detector.
And for patients who we are treating
a lung or a liver cancer or
something that's moving with
respiration,
as the chest moves up and down
this system detects that
breathing motion, so the two systems
then work together.
And then the whole robot moves over
and treats the patient
and then this part,
that arm will be fixed
and then the head will move with
respiration to follow the tumour.
And that's really what
makes this technology unique.
And we've got a nice mural on
the ceiling for patients to look at.
Known as "CyberKnife", the robot
will allow the team to use
far higher doses of radiation
per treatment session
than they have ever done before.
Lead radiographer Helen Taylor is
responsible for delivering
the treatment,
but before seeing real patients,
she has to test
every element of the machine.
It's a bit tricky in
a static patient,
because they don't
normally behave quite so well.
But it's all we can do at this stage
until we get the real thing.
The team have been preparing
for this for two years.
It's been an exciting project,
we've been doing our normal jobs
every day for years and years
and can do it in our sleep,
but this is new to us,
we've not done it before,
we've not given this kind
of dose with this technology before.
If we put that dose, for instance,
in the wrong place
we could do some serious harm,
so it's important we get it right.
The staff at the hospital
are pushing at the boundaries
of medicine, because cancer is
so notoriously difficult to treat.
The problem is that cancer is
a disease created by our own bodies.
Cancer isn't some sort of
alien invasion from outside
that has got into us,
it's actually our own cells.
And cancer is a consequence of what
happens to our own cells
when they go wrong and, in a sense,
it's kind of part of the price
we pay for being human and being
composed of all these cells.
Our cells are constantly dividing.
They grow, repair and replenish
our bodies.
It's an astonishingly
accurate process, most of the time.
Of course, not all our cells will
function normally all the time,
things will go wrong, and we need
to have a mechanism to get rid
of cells that aren't working
properly.
When cells go wrong, the body has a
particular way of dealing with them.
The cells can kill themselves.
It may sound strange, but this is
essential to keeping us healthy.
If cells don't die, and continue to
divide without stopping,
they can grow out of control,
creating cancer.
What we can see here is actually
cancer cells which are growing
in the laboratory.
So this is a film that's been
taken over a day or two,
obviously with time lapse.
It's chaotic, it's disorganised.
The cells, you get the impression,
are not really paying any heed to
what's going on around them.
And it's worth saying that actually
to even grow in the laboratory,
to grow in plastic in
the first place, is highly abnormal.
Once the cells have become
cancerous,
the body can no longer control them.
These are cells that become
very difficult to kill
and the way we would describe that
is being immortalised,
so the cells have the potential
to become immortal
and to grow forever, and that's
clearly a highly abnormal behaviour.
The ultimate aim of
a cancer treatment is to target
these abnormal cells,
leaving a patient's healthy cells
untouched, killing only the cancer.
For much of his adult life,
59-year-old Phil Garrard has
lived in the shadow of cancer.
Running is important, it takes
your mind off things, it relaxes you.
Once you get the heart pumping,
you always feel good afterwards.
I'm feeling fit and healthy
at the moment.
I don't feel any different to when
I was 20 years old, to be honest.
Phil has good reason to
worry about his health.
17 years ago, he witnessed
his father die from prostate cancer.
He was diagnosed, I think, too late
and the cancer had
spread to the bones.
And, I have to say,
it's a painful way to die.
It really shocked me.
It took him four or five years.
Yes, it wasn't good,
it wasn't a pretty sight.
It was so devastating that, in truth,
I think I ran away.
I couldn't cope with it.
To add to the pain
of his father's death, Phil was told
there was a chance
he too would develop the disease.
So, for the last 17 years,
he's been going for regular tests,
to pick up any early signs.
Three months ago, Phil and his wife,
Marie, received the latest results.
When we went that day to get
the results, do you remember?
We sat down and he said it
in the nicest possible way,
"Well, we found cancer." Yeah.
And for me, it was, "Wow, cancer,
the big C." I know. Total disbelief.
My head just went.
Because I just was obsessed almost
with what had happened to my father.
Having gone through the trauma of
that, I just said,
"I'm just repeating history now.
"Dad died of it,
and it looks like I'm going to."
And I just couldn't get myself
out of that thinking.
But now Phil has been given
the chance to leave
the shadow of his father's death
behind.
By having his prostate
removed in an operation at
the very forefront of
surgical development.
In the corner of
an ordinary operating theatre,
stands another extraordinary robot.
Known as the "da Vinci",
it's promising to change the way
prostate cancer surgery is
performed.
The robot is the pride and joy
of Chris Ogden,
one of the world's
most respected prostate surgeons.
He has pioneered this new
surgical technique in an attempt to
improve the experience of patients
undergoing surgery.
It means he must work in a very
different way to other surgeons.
Chris, why are you
taking your socks off?
Well, yes, most surgeons operate
with their socks on.
In fact, I used to, until I started
doing da Vinci surgery.
And it was after about three or four
months, when I was getting through
so many pairs of socks
with... For mysterious reasons,
they kept on getting holes in.
But it turns out that the pads
that prevent your feet from slipping
were causing my socks to wear
through, so now I operate barefoot.
Using the robot means Chris can
eliminate any natural tremor
from his hands.
And the tiny instruments are
highly manoeuvrable, allowing
delicate, accurate movements,
all without him
even touching the patient.
It was evolved for remote operating,
originally through a joint effort
between the American military
and NASA,
the theory being that it would offer
surgical expertise in space
without having to
send up your trained surgeon.
Chris is aiming to increase
the accuracy of surgery,
and using this technology, he hopes
to see his patients recover
more quickly from their operations.
In October 2010,
unfortunately there was evidence of
local recurrence at that site...
As new treatments are developed,
the doctors at the hospital must
decide just which treatment
is likely to help each patient.
..imaging, which was part of
the screening process...
Currently under discussion
is a revolutionary new drug they
have been trialling for treating
melanoma, a type of skin cancer.
The team have been inundated with
enquiries from patients.
There's an understandable demand from
patients to get access to this drug.
Given, in the last
sort of 10, 20, 30 years,
there haven't really been
any sort of major breakthroughs
in treating melanoma,
to actually be in a position
where we can talk about potentially
effective drugs to patients
for the first time
is a great position to be in,
so I'm not complaining.
For Dr James Larkin,
it's crucial that his team ensures
the right patients receive
this new drug.
..progression in the interim.
Fine, OK, thanks very much, Angela.
So, the next patient, Alison?
I spoke to her yesterday,
she's fine...
They must be careful that
the benefit to the patient is
great enough to outweigh
any risks from side effects.
..she's feeling a lot better and
she's weaning off the steroids.
So the plan is we're going to see
her in clinic this afternoon
and consider her for PLX4032 in
the expanded access programme,
if everybody agrees?
OK, thanks very much, everybody,
I think that's it.
So we can go to clinic. Cheers.
The new drug, Vemurafenib,
is not yet widely available,
but could help around half of people
with the very worst cases
of melanoma.
For retired teacher, Rosemary Reid,
the new drug offers a ray of hope.
She was diagnosed with
malignant melanoma four years ago.
It was devastating
because it just was a whole
new, unknown, fearful thing
that was in my life, which
I hadn't ever come across before.
Rosemary's illness has forced her to
end a lifelong passion,
travelling the world.
Over the last four years,
she's undergone both surgery
and chemotherapy.
One of the strange things
about cancer treatment is
that it's a bit like backpacking
round Vietnam or something,
you don't know what's going to
happen in three days' time.
It might be good, it might be bad,
but let's hope it's good.
Despite the best efforts
of the doctors, the cancer returned.
It has now spread to
her internal organs.
The lesions had spread to different
parts of my liver and I've
now got it all over my liver,
and so I couldn't have an operation.
And it had also spread into my lungs
as well, not so much.
Um, so I couldn't have the operation.
So it was decided that I would have
dacarbazine as a chemo treatment.
So I had two sessions of that to see
if it was going to work,
and it didn't have any effect at all,
the lesions are still growing.
And we realised that, actually,
when cancer gets to that stage
that it's sooner or later terminal,
and that was a very hard thing
to come to terms with and, um...
to tell our children, really.
For decades, medicine didn't have
much to offer patients like
Rosemary.
But now there's a real sense
of optimism about the potential
of this new drug.
Working with Dr James Larkin
on the trial
is the hospital's medical director,
Professor Martin Gore.
We're really very excited,
it's a real -
that rather over-used word -
breakthrough, for melanoma.
I wasn't entirely sure I was going
to see it in my professional life,
but I have, and it's
really tremendously exciting.
Rosemary and her husband, Peter,
have travelled into the hospital,
because the team have discovered
she's one of the 50% of patients who
could respond well to the drug.
Without treatment, Rosemary may
only have months to live.
KNOCK ON DOOR
Come in.
Hello, nice to see you
again.
Hello, take a seat. Hello.
Hello, nice to see you again.
So, are we all set? I hope so.
You've read the information sheet?
Yes.
Do you understand what taking
the drug entails?
I think so, yes. I'll take pills
twice a day and hopefully
it will reduce the tumours that
I have in my liver and in my lungs.
So it's got a very good chance
of either stabilising the disease
or causing some shrinkage.
And there's about a 50% chance
that it will cause substantial
shrinkage of the tumours,
which would be very good.
That's very good news.
Do you understand about
the side effects?
I understand that they are mainly
connected with skin and that
I mustn't be in the sun too much,
or at all,
and that there can be some rashes.
Probably the other main side effect
is a bit of fatigue.
But not in any serious way.
Yes, yes.
So Rosemary would be bonkers
not to take it?
The answer is yes!
And you're probably going to say
I would say that, wouldn't I?!
But actually, there are treatments
that we give where
we have very long conversations
about whether it's worth it or not.
But I think, in this case,
it's one of those occasions where
we can put our hand on our heart
and say, look,
you really should take it.
And we're going to start today.
Carla has already got the drugs
ready for you. OK?
Yes, that's fine. They are the drugs.
Lovely, fine...
This revolutionary drug fights
cancer in a new and powerful way.
It's one of the new generation of
drugs that have been made possible
by a vast improvement in
our understanding of what cancer is.
Cancer occurs when our cells
divide out of control
and develop the potential to become
immortal.
This happens because the DNA,
the genes at the very heart
of the cell, have gone wrong.
It's Professor Naz Rahman's job to
hunt down those defective genes.
BEEPING
We get DNA,
from individuals who've had cancer,
and then we sequence that genetic
code, and then we compare that
with similar data from people who are
well, who haven't had cancer,
so we can look to
see what the differences are there.
So that we can try to identify
what may be the causative genes
that have led to
that person developing cancer.
In some cases,
faulty genes are inherited,
and can increase
the likelihood of getting cancer.
But less than 10% of cancers are
caused by inheriting faulty genes.
The majority of cancers are not due
to something that's been inherited,
they're due to genetic changes
that have
happened during life in a particular
set of cells that then start
growing uncontrollably
and become a cancer.
These types of genetic faults can
happen to any of us, at any time.
There are certain things
that increase
the likelihood of that kind
of damage occurring, for example,
UV light can make that happen
more likely, the carcinogens in smoke
also lead to DNA being damaged.
In fact, just as we get older,
we gradually accumulate more changes
in our DNA and that's part of
the reason why you are more likely
to get cancer as you get older.
Naz's team is part of a worldwide
network of genetic scientists,
carefully decoding our DNA.
Looking for a fault among the six
billion letters in the human genome
is like looking for
a needle in a haystack.
But finding one is crucial to
developing
a genetically targeted drug.
You get a sense that
when you're making that discovery,
just at that moment at least,
you're the first person that knows
that that gene has caused
that disease, and also you have
an insight into the hope that
that's going to be useful
down the line in terms of helping
patients getting better treatments.
Discoveries like these have
triggered
a revolution in cancer treatment.
The promise that, one day,
if we are struck down by cancer,
keeping it at bay could be as simple
as taking some pills.
The process of hunting for genes has
led to the new melanoma drug
they've been trialling
at the Royal Marsden.
The question now is whether
these innovative new treatments
will deliver the results
they are hoping for.
WHIRRING
After six weeks,
the radiotherapy team have completed
the installation of their robot.
And Dr Nick Van As has begun to
look for suitable first patients.
..50, 55 minutes...
Ray Dean has come to find out
whether he may be eligible
for the treatment.
I don't know whether or not
it's going to be suitable for me
until I see the consultant.
As I say, hopefully they're going
to be able to do it
and, hopefully, that's going to
give me a bit of extra life.
Ray's cancer has spread to
a lymph node.
Unfortunately, it is not operable,
and he has already had the maximum
amount of standard radiotherapy.
But now there is a chance that
the new technique could offer
a crucial lifeline.
Mr Raymond Dean?
It all depends on
Ray's latest scan results.
If the cancer has spread
beyond the lymph node,
it will be too late for
the treatment to go ahead.
Hi, have a seat, nice to see you
again. So, you've had the scan.
Do you want to just go over
the rationale for doing the scan,
do you understand why we did it?
Yes, basically to see
if it was just in the one place.
Yes, OK, so...
And is it just in the one place?
It is. Oh, thank God for that!
That's the first bit of good news.
It's been a really informative scan.
I'll show you the pictures.
That node that we saw on the CT is
this little orange blob that
lights up.
But what we wanted to see was,
did it light up, because if it did
it's very highly suggestive
that that is prostate cancer,
and the other thing is that nothing
else lit up, and nothing else has.
This lymph node is very close to
the area we irradiated before
and that's why we weren't
particularly keen on giving you
standard radiotherapy again.
But I think we can do this,
we can give that a very high dose,
using the CyberKnife, and really
minimise the dose elsewhere.
But there's not no risk, I'm afraid.
Oh, yeah.
I think the risk we can make is
relatively low, but there is a risk.
Yes. But I think it's worth doing.
Definitely.
For Ray and his wife, Janet, it's
an end to weeks of anxious waiting.
'I'm lost for words, really.'
Yes, you know. You come up here very
hopeful that everything's going to
come out right,
and, you know, this CyberKnife has
come along at just the right time.
Six months ago, I wouldn't
have been offered the treatment.
It's good news for us.
Despite it all glowing up there.
And you know, I told you
I'd glow in the dark. Yes!
But...
Well, we've got a few more years to
do caravanning, haven't we?
Well, that's right, yes,
I mean to say, yeah,
absolutely overjoyed, brilliant.
Following his scan results,
the team have decided Ray will be
their very first patient.
And for Nick, the reality of what
they're about to do
is beginning to sink in.
Now that I'm talking to
real patients about treating on
the CyberKnife,
I must say for the first time in
the whole process, I've got nervous,
so now I realise that we're going to
be doing something we've
not done before,
and this is for real.
I'm confident we can do this,
and we can do it safely,
but I will be quite relieved when
the first treatments are behind us.
MURMUR OF CONVERSATION
You have to set a VOI,
but you can set a very broad...
Nick must now start to design
a unique treatment plan
specifically for Ray.
To do this,
he calls on a team of experts.
As well as the doctors
and radiographers,
there are full-time physicists
whose job it is to work out
exactly how the robot will move
around Ray to deliver the radiation.
We're going to force the target dose
into the shell, aren't we?
Yeah, you need... You can't
mix and match structures.
Right now we have no idea what
is the right steps to follow.
So the role of defining the areas
we want to and don't want to treat
is the doctors', and the physicists
then create the plan for us.
The workhorses and the brains.
That's nice!
Which way round was that, Nick?
THEY ALL LAUGH
The physicists are the brains here!
Because the level of radiation
is so much higher
than they would usually
give a patient like Ray,
their plan must be
extremely precise.
If they get it wrong, it could cause
serious damage to Ray's body.
Using scans of Ray's abdomen,
the doctors create a 3D model to see
where to avoid and where to target.
As the plan takes shape,
it's possible to see clearly
what makes this type
of treatment different.
What we're looking at now
is the radiation plan.
These lines represent the angles
or the number of beams
that are coming in
in order to create the dose.
As opposed to a normal plan,
which we just have dose
just coming in from maybe the sides
and one from the front,
you can see that there's loads,
hundreds of lines going in.
By splitting the overall radiation
into individual beams,
delivered from different angles,
each beam only delivers a low dose,
causing less damage
to healthy tissue.
This approach to radiotherapy
has huge potential advantages.
So if you just use three beams,
you've got to put about 30%,
33% of the dose from each beam.
If you're using 100 beams,
you're only going to put 1%
of the dose, theoretically,
so you put a very little amount
of dose through each beam
but the centre is hot.
Radiation is concentrated
on the target
and falls quickly away either side.
At a centimetre distance, the dose
is just 10% of the full amount.
If we did this with standard
radiotherapy, we'd still be
at 50-60% of the dose in that region,
possibly even higher.
So we want this very rapid
fall-off of dose,
and that's what we've achieved
by using all these beams
converging on one target.
In less than 24 hours
this plan will become reality,
as Ray becomes the hospital's
first patient
to be treated with the robot.
You realise there's a lot
of responsibility now
to make sure this goes right.
I wouldn't say I'm stressed about it,
but I want tomorrow to come
and tomorrow to go!
But we'll get there, you know.
Today's about making sure
the plans are correct,
and we'll probably be here
quite late into the evening.
For Phil, the waiting is over.
He's travelling into the hospital
for his operation
on the da Vinci surgical robot.
Goodbye, house. Next time I see you
I'll be without a prostate.
If it goes well,
he could be cancer-free.
'It's almost like you feel
you're going round with a label.
'There's this burden,
there's this tag on you saying,
'"This is Phil
and he's got cancer."
'So I want to get to a point
where I can go round
'and think to myself,
"No, I'm Phil without cancer,"
'and just move on.'
All right? I'll need that!
Put your bag down there and make
yourself comfortable. OK. Thank you.
Before the robot
can be put in place,
the surgical team need
to make preparations
to insert the instruments
and inflate Phil's abdomen
with carbon dioxide
to create space
for the robot to work.
The robot can now be brought in
to replace Chris Ogden
at the operating table.
That's good.
Make sure we don't clash the arms.
Great.
Great.
That's just placing
the instruments inside the patient,
and...the robot's engaged.
Across the room, Chris takes
his position at the console...
Thank you.
..and the operation can begin.
The mechanical movements of
his hands are scaled by the robot,
then translated into precise
micro-movements of the instruments
inside the patient.
He can switch between
three instrument arms
and operate the camera
with a foot pedal.
The camera arm contains
two high definition cameras,
which together give a 3D view,
enabling Chris to get
a sense of depth and perspective.
You start to feel you really are
inside the space,
which is an amazing feeling, really,
because that's exactly
where you want to be as a surgeon -
right in where the action is.
You become part of it
and it becomes part of you.
Prostate surgery is particularly
difficult because all of the cancer
must be removed without damaging any
of the close-lying nerves or organs.
Any complications could leave
the patient impotent or incontinent.
The precision of the robot
promises to reduce these risks.
So now we take this, which is
the prostate. That goes into a bag,
which we'll retrieve
when we remove the instruments.
Just like obstetrics.
And there's our prostate.
The operation is over
and Phil is taken to recovery.
When patients have their prostate
removed with open surgery,
they can expect to stay
in hospital for up to a week.
But because this procedure
is less invasive,
Phil is discharged
in less than 24 hours.
In three months' time,
tests will reveal
what effect the operation has had.
For some people, even the very best
surgery is not an option.
Rosemary Reid is one of
the first patients to be given
a ground-breaking new drug
for melanoma.
She hopes it will extend her life.
We're very lucky
that we're part of the trial
and we're hoping that it will improve
things, and that we will be...
or that I will be one of
the lucky ones that it works for.
Rosemary had two bouts
of chemotherapy
and they didn't work,
so now we've got some hope.
Yep. So...
We'll take it from here
and hope that it will work.
Many of the new treatments being
pioneered at the Royal Marsden
evolved out of work done here,
at the Institute of Cancer Research.
The drug that Rosemary is taking
was the result of an international
collaboration of scientists
and close to
£1 billion of investment.
It began with the hunt for a gene
that drives melanoma.
After looking at hundreds of samples
from melanoma patients,
geneticists made a major discovery.
They found that one gene was mutated
in about half of the patients,
but was normal in healthy people.
It was a gene called BRAF.
About half of the melanomas will have
that specific change in BRAF.
If you look at the DNA
in normal individuals,
you will almost never see
that change.
So what that's telling you
is that that isn't chance.
That there is a specific causal
relationship, is what we call it.
That change in that gene
is critically important
for why those cells
have become melanoma cancers.
People with melanoma are far more
likely to have the mutated BRAF gene
than healthy people, and scientists
here played a key part
in turning this knowledge
into a treatment.
We have the green China tea,
very nice.
Jasmine with flowers. That's very
nice, that smells nice, actually.
Darjeeling, rooibos,
Earl Grey and Ceylon.
(I don't like Earl Grey.)
When Naz's colleague,
Professor Richard Marais,
heard about the mutation,
he knew it was a major find.
When I heard that BRAF was
mutated in half of human melanomas,
I was beside myself with excitement,
because that really tells you
that here,
probably for the first time,
we're starting to understand the
processes that drive the formation
of this one type of cancer.
I think it's very difficult to try
and convey how exciting that was.
His day-to-day work involved
studying normal cell division,
and he suspected the BRAF gene
was involved in that process.
If the BRAF gene was mutated,
he thought that might cause
the cell division to go wrong,
triggering cancer.
To test his theory,
he removed the mutated BRAF
from some melanoma cells in his lab
and amazingly, the cancer cells
stopped dividing and died.
That tells you then that
this is not just a silent passenger
that's not doing anything
in the cancer.
It tells you that
it's what's driving the cancer.
It really speaks to you
and says, "This is where
you should be putting your effort."
He began to examine
the damaged BRAF gene further.
The normal BRAF gene
produces a protein
which activates cell division.
And it is this protein
that's critically important
in the cancer cells.
This is actually the shape
of the BRAF protein,
and what you can see is that
it's got lots of lumps and bumps,
but the most important part
of the molecule is this, here.
You can see this very deep cleft
that really runs into
the heart of the protein,
and that's the business end
of the molecule.
In the normal BRAF protein,
this cleft is closed off
unless the cell needs to divide.
Now, the problem with the mutant
form of BRAF, what we discovered
is that the gate won't close, so the
protein remains active all the time.
I think I can actually illustrate it
using this tea caddy here.
You see that it's got
this nice catch on it.
If we imagine that this is
the BRAF protein,
this is the cleft on the inside,
and by locking the tea caddy,
we can turn the protein off
and keep it off.
But when this catch is broken,
the protein stays open all the time.
It's constantly active
and constantly driving
the growth of the cancer cells.
So then we need to develop drugs
to stop that protein from working.
We can use these tea bags
to illustrate the drug
and the idea is that if we put
enough of these tea bags in here,
we'll block up the cleft and that'll
stop the protein from working
and that means that the cells
won't be forced to proliferate.
Lipophilic pocket, which is...
The next step in developing
any genetically targeted drug
is for the drug designers
to find a chemical which can block
the cavity in the crucial protein.
For Professor Paul Workman,
designing a drug
can be a problem of geometry,
and it is being transformed
by the latest 3D technology.
So what we're looking at here
is the surface of the protein,
a small part of it - the bigger
protein surface is all around here.
In this cavity is the essential
part of this molecule
that makes it cause cancer.
With the target identified,
Paul and his team screen
over 100,000 chemicals,
to see if any show signs
of binding into the cavity.
When they find one with potential,
they turn it into a virtual model.
Here you can see it fills
quite a bit of the cavity,
but not as much as we would like.
It did actually have some anti-cancer
activity, albeit quite weakly, and we
needed to make it more effective.
Using the 3D model,
the team can fine-tune the drug,
atom by atom,
to perfectly fit the entire cavity.
So here you can see the structure
of the much more advanced compound.
You can see it's a more complex
structure, it's bigger,
there's more complexity in geometry,
and as a result
it binds much more effectively.
This drug was 1,000 times
more effective on the cancer cells
than the original hit.
This 3D technology makes
the development of a drug
faster and more efficient
than can be achieved
in the lab alone.
There's a beauty to this
which is absolutely captivating.
I continue to be delighted by seeing
the beauty of the interaction.
Finally, you've got
the best satisfaction,
which is that patients
will benefit from that science.
It's hard to beat.
HE LAUGHS
As more and more genes responsible
for driving cancer are discovered,
scientists will be able to design
increasing numbers
of targeted drugs.
The ambition is that in the future,
there will be drugs
to act on every type of cancer.
There's a picture of the day.
Now, I can't find one.
It's the morning of Ray Dean's first
robotic radiotherapy session
and the start of a treatment,
which he hopes will extend his life.
Some of it is just the waiting,
going back to the old days,
when you're playing football,
tension all builds up inside you.
Once you get on the pitch there,
completely different. It just goes.
Once you're out there,
then it's all gone.
So I suppose, you know,
this is the same thing.
FAINT BEEPING
For the last two days,
the radiotherapy team have been
running final tests.
Not everything has gone smoothly.
You'll have to come round
and let him in.
Hugh, this...
This is a whole series
of error messages that's trying to,
we're just trying to turn it all off
and reboot it and start again,
which is very frustrating.
I think it's got stage-fright
this morning. I know.
Even a machine this sophisticated
sometimes needs switching off
and on again.
WHIRRING
The pressure must be on everybody
involved at the Marsden,
as well as myself and, um...
let's hope everything goes well.
A, B and C...
I'll go and find the case. OK.
Just sorting out the music.
After years of planning
and months of preparation,
this robot is about to deliver
radiation to a patient
for the very first time.
Put your hand up if you need to say
anything, we'll come through.
Cheers. Thank you.
CONTINUOUS BEEPING
Is that everybody?
OK, so we'll see
you at the end.
Mmm. About an hour,
we'll see you then.
For the next 45 minutes,
the robot delivers the highest
dose of radiation
they've ever given a patient
like Ray.
Because of this, his treatment
will take only three sessions.
A dramatic improvement on the 35
sessions of radiotherapy
he had before.
In four weeks' time,
a blood test will reveal
if the treatment has begun
to take effect.
Phil Garrard is back out
running with his sons,
three months after his operation
with the surgical robot.
He has been given the results
of his blood test,
which will reveal if his prostate
cancer is still there.
They said the result
was unrecordable,
which is what I think everybody's
looking for.
It wasn't even on the scale.
So the lower it is, the better,
but mine was unrecordable,
because it was so low.
You get confidence that they've
cracked this horrible disease
and it's not a thing to be
so fearful as it used to be.
The development of robotic surgery
is promising to increase precision
and dramatically reduce recovery
times for patients of the future.
Two months ago,
Ray Dean was hoping a new form
of radiotherapy
would extend his life.
He's now here for the results
of his PSA blood test,
a measure of the level of cancer
that remains.
Well, the good news...
The good news?
It's worked well.
The PSA has
fallen from 21 to 5.6. So..
That's absolutely amazing.
We couldn't have wished for better
news. No, it's great, I'm delighted.
I have to be honest,
I was quite nervous...
LAUGHTER
Yes, yeah, yeah. So, very relieved.
As I said to you,
it's probably earlier I normally
would be checking it,
although there isn't really
a normal for us in this. No, no.
So, but I mean, that's, I hope
that it will continue to fall. Yes.
So to be so much lower
in such a short period of time,
it's exactly what we wanted to see.
Yes. That's absolutely brilliant.
Over the moon. Over the moon.
I had every confidence,
but it's nice to actually hear
that it has worked.
Yeah. And so well.
The good thing is there that,
as the doctor said, you know,
I'm the first one and, you know,
they're hoping for a good result,
which is what they've got, and I mean
to say, I've got a good result.
So, it's celebrations time.
LAUGHS
It's great to have the very
first patient we treated
with a good outcome.
As I said, it's very early days,
but it's great to have a good
outcome on number one.
The fact that it's had such a
significant fall,
you know, suggests the decision we
made to do it was the right one
and the fact that
he's almost more pleasingly,
he's had no problem
with the treatment.
He's perfectly well and he's
continuing to work full time
and it hasn't really appeared
to impact his quality of life
at all.
For Nick, this is just the
beginning.
He is comparing the procedure
to standard radiotherapy
in a series of trials,
and plans to start treating
a wider range of cancers.
Two months after starting
on the genetically-targeted drug,
Rosemary Reid is back for her scan,
to see if it has had any effect.
'Scans are always little
peaks in one's treatment
'and it's scary having the results.'
Can I just get you to confirm
your full name and date of birth?
Unfortunately, after a week
of taking the pills,
Rosemary developed some side effects
and had to have a temporary
break in her treatment.
Bring your arms right above
your head for me.
'I'm not sure how much
success I'll have,
'because I've had to be off
for three weeks
'because of the rashes I had.'
Breathe normally.
'So, it may not show
to be as effective as I'd hoped.
'It was very, very disappointing
to have to come off it,
'because I thought,
I'm losing time here.
'You know, all this time
the tumour is growing,
'and coming off it was the last
thing I wanted to do.'
It's all finished.
24 hours later,
in the melanoma clinic,
Dr James Larkin
has Rosemary's results.
Hi.
Hello, nice to see you again.
Nice to see you again as well.
Hi.
Thank you. Nice to see you again
as well, sir.
Have a seat, James, please.
So, the scan was good.
Oh, really?
That's the most important thing
of all. Fantastic.
So, definite shrinkage of pretty
much all of the abnormalities
we could see in the liver,
significant shrinkage.
That is fantastic,
as I really didn't think
there would be any change
after the reduction
in the dose.
Oh, really? Yes.
No, no, no. Definitely dramatic
shrinkage, really.
And certainly in the lungs,
some of the abnormalities
have disappeared altogether.
So it's great.
Wow, that's fantastic.
What you can see here is a scan
just before you started treatment,
and then the scan from yesterday.
And these sort of black
areas are the lungs.
For example, there, you see
that sort of spot there,
that's a bit of melanoma in the
lungs before you started treatment
and then there,
I can't really see it at all.
And, in fact, most of the
abnormalities in the lungs
have pretty much disappeared
altogether,
which is obviously great news.
And then if we were to look
at the liver,
which is the other main place that
we know there are abnormalities,
you see the sort of darker
grey areas,
those are the lumps of melanoma
and then if we look at a scan
from afterwards... Good lord.
..you can see there,
it's pretty much half the size.
The other ones have got smaller
as well. Pretty much everything,
everything you look at
is smaller.
So it's wonderful.
That's wonderful news.
So it's nice to be able
to tell you that...
To actually see a reduction
was fantastic. Mm-hm.
Because, it was just like
a surprise.
It was like getting
As for A-level
when you thought you were
going to get all Cs.
It was brilliant,
absolutely wonderful news.
..side effects. Yes, yes...
'Really for the last 20
or 30 years,'
discussing scan results
with patients on treatment,
nine times out of ten,
it would be a conversation
about how the scan is worse
and it's almost the opposite now.
Eight or nine times out of ten
with this treatment,
you can say to the patients,
things have got better
which is a great feeling,
particularly on a background
of so little progress
treating this disease, really,
since the 1970s.
It's given us a lot of time,
yes, I think so. Yes.
Shall we go to Nepal
at the end of October?
We could do, yes.
SHE LAUGHS
Yes, no, it certainly means
we can plan for the future more now
and look forward to things,
and...yeah.
So I shall not give my
winter clothes to Oxfam.
Too right. I shall buy
some new ones. Yeah.
Rosemary will keep taking
the drug for as long as it
continues to work.
It's not yet a complete cure,
but drugs like these,
based on understanding cancer,
offer our greatest hope that one day
we'll be able to defeat
this disease.
We have to be cautious
about all these claims
that the cure is
just around the corner.
Cancer is a remarkably
complicated problem,
but we should understand
that progress is being made.
Understanding exactly
what's causing cancer
means that more
drugs can be created,
with the promise of increased
life expectancy and future cures.
In the next five to ten years,
I think we'll have catalogued
pretty much all of the cancer genes,
we'll have a very good understanding
of exactly how they work
and how they interact with each
other to cause cancer
and develop inhibitors
against the majority of those.
By combining technology
with scientific knowledge,
the future of cancer treatment
looks better for us all.
We are making inroads
at multiple different levels.
So, from a genetic level to a drug
development level,
to accurately delivered radiation,
or surgical techniques,
I think it's a great time to be
working in the field
and I think we'll actually try and
target tumours more scientifically
and give us a much better chance
of eradicating the cancers
than we have done in the past.
Subtitles by Red Bee Media Ltd
all of our lives.
A disease whose diagnosis can be
devastating.
One of the hardest things was
actually telling the family,
especially our three children.
More than one in three of us
will get it in our lifetime.
Nobody knows if it's going to be
the last Christmas,
the last birthday, the last holiday,
and it's just that uncertainty.
Cancer is one of the most complex
diseases to treat,
because it's a part of us.
Cancer isn't an alien invasion
from outside,
it's actually part of the price
we pay for being human.
This programme follows three people
through
one of the most difficult times
of their lives.
I'm just repeating history now.
Dad died of it
and it looks like I'm going to.
Horizon has been given unprecedented
access behind the doors
of the Royal Marsden Hospital
in London,
where they are pioneering
some ground-breaking new treatments.
This is new to us, we've not done it
before, we've not given
this kind of dose,
with this technology.
On the day,
it will be nerve-wracking.
For Ray, Phil and Rosemary,
these treatments offer new hope.
And for all of us,
they hold the possibility that we
could one day defeat cancer.
It's summer 2011.
And Ray Dean is about to face
the biggest challenge of his life.
I used to be a professional
footballer,
played against some of
the best footballers in the country.
The most famous being Georgie,
Georgie Best.
And, er, yeah, played at Liverpool.
On the famous turf at Anfield,
in the cup match, yeah.
That was in the, erm,
in the younger days.
Seven years ago, Ray was diagnosed
with prostate cancer
and underwent an intensive
period of radiotherapy treatment.
It was seven weeks, five days a week,
I had 35 sessions.
So I started at about five o'clock in
the morning so that I could do
a bit of work, earn a bit of money,
and then go up there for
the treatment.
His treatment held the cancer at bay
for nearly five years.
But then Ray received the news
he'd been dreading -
the cancer had returned.
You get more and more confident
as the years go by that it's not
going to come back, but,
unfortunately, it has come back.
This time, Ray's options
for treatment are limited.
Now, his best hope lies with radical
developments in cancer medicine.
Hopefully, everything's going
to be all right.
I don't think the nerves will kick
in, I'm too old to have nerves now!
So, erm, yes.
It's just the build-up.
This robot could offer Ray
some hope.
It's part of a new generation
of advanced radiotherapy machines,
one of only a handful of its type
in the UK.
In charge of getting it
up and running is Dr Nick Van As.
Radiation remains the most effective
way of killing a cancer cell.
We could kill all cancer cells if
we could give them enough radiation,
the problem is we'd have to spare
the normal tissue around it.
So, the challenge is to get the
high dose of radiation to a cancer
and minimise the dose to
those surrounding tissues.
The robot is the newest arrival at
the Royal Marsden Hospital in
London.
Together with
its scientific partner,
the Institute of Cancer Research,
the hospital pioneers and
researches cutting-edge treatments.
It's nice to be working in a place
where we have the ability to invest
in new techniques and be, hopefully,
at the forefront of
developing where treatments
are going to be in ten years' time.
This robot is the hospital's latest
way of using radiation to kill
cancer cells.
It targets the cancer with
pin-point accuracy,
even as a patient moves
and breathes.
On the ceiling you can see that
there's two X-ray units,
one on each side, that's
for visualising the tumour, and then
that allows the robot to correct for
movement of the tumour in real time.
And then this over here is
a light detector.
And for patients who we are treating
a lung or a liver cancer or
something that's moving with
respiration,
as the chest moves up and down
this system detects that
breathing motion, so the two systems
then work together.
And then the whole robot moves over
and treats the patient
and then this part,
that arm will be fixed
and then the head will move with
respiration to follow the tumour.
And that's really what
makes this technology unique.
And we've got a nice mural on
the ceiling for patients to look at.
Known as "CyberKnife", the robot
will allow the team to use
far higher doses of radiation
per treatment session
than they have ever done before.
Lead radiographer Helen Taylor is
responsible for delivering
the treatment,
but before seeing real patients,
she has to test
every element of the machine.
It's a bit tricky in
a static patient,
because they don't
normally behave quite so well.
But it's all we can do at this stage
until we get the real thing.
The team have been preparing
for this for two years.
It's been an exciting project,
we've been doing our normal jobs
every day for years and years
and can do it in our sleep,
but this is new to us,
we've not done it before,
we've not given this kind
of dose with this technology before.
If we put that dose, for instance,
in the wrong place
we could do some serious harm,
so it's important we get it right.
The staff at the hospital
are pushing at the boundaries
of medicine, because cancer is
so notoriously difficult to treat.
The problem is that cancer is
a disease created by our own bodies.
Cancer isn't some sort of
alien invasion from outside
that has got into us,
it's actually our own cells.
And cancer is a consequence of what
happens to our own cells
when they go wrong and, in a sense,
it's kind of part of the price
we pay for being human and being
composed of all these cells.
Our cells are constantly dividing.
They grow, repair and replenish
our bodies.
It's an astonishingly
accurate process, most of the time.
Of course, not all our cells will
function normally all the time,
things will go wrong, and we need
to have a mechanism to get rid
of cells that aren't working
properly.
When cells go wrong, the body has a
particular way of dealing with them.
The cells can kill themselves.
It may sound strange, but this is
essential to keeping us healthy.
If cells don't die, and continue to
divide without stopping,
they can grow out of control,
creating cancer.
What we can see here is actually
cancer cells which are growing
in the laboratory.
So this is a film that's been
taken over a day or two,
obviously with time lapse.
It's chaotic, it's disorganised.
The cells, you get the impression,
are not really paying any heed to
what's going on around them.
And it's worth saying that actually
to even grow in the laboratory,
to grow in plastic in
the first place, is highly abnormal.
Once the cells have become
cancerous,
the body can no longer control them.
These are cells that become
very difficult to kill
and the way we would describe that
is being immortalised,
so the cells have the potential
to become immortal
and to grow forever, and that's
clearly a highly abnormal behaviour.
The ultimate aim of
a cancer treatment is to target
these abnormal cells,
leaving a patient's healthy cells
untouched, killing only the cancer.
For much of his adult life,
59-year-old Phil Garrard has
lived in the shadow of cancer.
Running is important, it takes
your mind off things, it relaxes you.
Once you get the heart pumping,
you always feel good afterwards.
I'm feeling fit and healthy
at the moment.
I don't feel any different to when
I was 20 years old, to be honest.
Phil has good reason to
worry about his health.
17 years ago, he witnessed
his father die from prostate cancer.
He was diagnosed, I think, too late
and the cancer had
spread to the bones.
And, I have to say,
it's a painful way to die.
It really shocked me.
It took him four or five years.
Yes, it wasn't good,
it wasn't a pretty sight.
It was so devastating that, in truth,
I think I ran away.
I couldn't cope with it.
To add to the pain
of his father's death, Phil was told
there was a chance
he too would develop the disease.
So, for the last 17 years,
he's been going for regular tests,
to pick up any early signs.
Three months ago, Phil and his wife,
Marie, received the latest results.
When we went that day to get
the results, do you remember?
We sat down and he said it
in the nicest possible way,
"Well, we found cancer." Yeah.
And for me, it was, "Wow, cancer,
the big C." I know. Total disbelief.
My head just went.
Because I just was obsessed almost
with what had happened to my father.
Having gone through the trauma of
that, I just said,
"I'm just repeating history now.
"Dad died of it,
and it looks like I'm going to."
And I just couldn't get myself
out of that thinking.
But now Phil has been given
the chance to leave
the shadow of his father's death
behind.
By having his prostate
removed in an operation at
the very forefront of
surgical development.
In the corner of
an ordinary operating theatre,
stands another extraordinary robot.
Known as the "da Vinci",
it's promising to change the way
prostate cancer surgery is
performed.
The robot is the pride and joy
of Chris Ogden,
one of the world's
most respected prostate surgeons.
He has pioneered this new
surgical technique in an attempt to
improve the experience of patients
undergoing surgery.
It means he must work in a very
different way to other surgeons.
Chris, why are you
taking your socks off?
Well, yes, most surgeons operate
with their socks on.
In fact, I used to, until I started
doing da Vinci surgery.
And it was after about three or four
months, when I was getting through
so many pairs of socks
with... For mysterious reasons,
they kept on getting holes in.
But it turns out that the pads
that prevent your feet from slipping
were causing my socks to wear
through, so now I operate barefoot.
Using the robot means Chris can
eliminate any natural tremor
from his hands.
And the tiny instruments are
highly manoeuvrable, allowing
delicate, accurate movements,
all without him
even touching the patient.
It was evolved for remote operating,
originally through a joint effort
between the American military
and NASA,
the theory being that it would offer
surgical expertise in space
without having to
send up your trained surgeon.
Chris is aiming to increase
the accuracy of surgery,
and using this technology, he hopes
to see his patients recover
more quickly from their operations.
In October 2010,
unfortunately there was evidence of
local recurrence at that site...
As new treatments are developed,
the doctors at the hospital must
decide just which treatment
is likely to help each patient.
..imaging, which was part of
the screening process...
Currently under discussion
is a revolutionary new drug they
have been trialling for treating
melanoma, a type of skin cancer.
The team have been inundated with
enquiries from patients.
There's an understandable demand from
patients to get access to this drug.
Given, in the last
sort of 10, 20, 30 years,
there haven't really been
any sort of major breakthroughs
in treating melanoma,
to actually be in a position
where we can talk about potentially
effective drugs to patients
for the first time
is a great position to be in,
so I'm not complaining.
For Dr James Larkin,
it's crucial that his team ensures
the right patients receive
this new drug.
..progression in the interim.
Fine, OK, thanks very much, Angela.
So, the next patient, Alison?
I spoke to her yesterday,
she's fine...
They must be careful that
the benefit to the patient is
great enough to outweigh
any risks from side effects.
..she's feeling a lot better and
she's weaning off the steroids.
So the plan is we're going to see
her in clinic this afternoon
and consider her for PLX4032 in
the expanded access programme,
if everybody agrees?
OK, thanks very much, everybody,
I think that's it.
So we can go to clinic. Cheers.
The new drug, Vemurafenib,
is not yet widely available,
but could help around half of people
with the very worst cases
of melanoma.
For retired teacher, Rosemary Reid,
the new drug offers a ray of hope.
She was diagnosed with
malignant melanoma four years ago.
It was devastating
because it just was a whole
new, unknown, fearful thing
that was in my life, which
I hadn't ever come across before.
Rosemary's illness has forced her to
end a lifelong passion,
travelling the world.
Over the last four years,
she's undergone both surgery
and chemotherapy.
One of the strange things
about cancer treatment is
that it's a bit like backpacking
round Vietnam or something,
you don't know what's going to
happen in three days' time.
It might be good, it might be bad,
but let's hope it's good.
Despite the best efforts
of the doctors, the cancer returned.
It has now spread to
her internal organs.
The lesions had spread to different
parts of my liver and I've
now got it all over my liver,
and so I couldn't have an operation.
And it had also spread into my lungs
as well, not so much.
Um, so I couldn't have the operation.
So it was decided that I would have
dacarbazine as a chemo treatment.
So I had two sessions of that to see
if it was going to work,
and it didn't have any effect at all,
the lesions are still growing.
And we realised that, actually,
when cancer gets to that stage
that it's sooner or later terminal,
and that was a very hard thing
to come to terms with and, um...
to tell our children, really.
For decades, medicine didn't have
much to offer patients like
Rosemary.
But now there's a real sense
of optimism about the potential
of this new drug.
Working with Dr James Larkin
on the trial
is the hospital's medical director,
Professor Martin Gore.
We're really very excited,
it's a real -
that rather over-used word -
breakthrough, for melanoma.
I wasn't entirely sure I was going
to see it in my professional life,
but I have, and it's
really tremendously exciting.
Rosemary and her husband, Peter,
have travelled into the hospital,
because the team have discovered
she's one of the 50% of patients who
could respond well to the drug.
Without treatment, Rosemary may
only have months to live.
KNOCK ON DOOR
Come in.
Hello, nice to see you
again.
Hello, take a seat. Hello.
Hello, nice to see you again.
So, are we all set? I hope so.
You've read the information sheet?
Yes.
Do you understand what taking
the drug entails?
I think so, yes. I'll take pills
twice a day and hopefully
it will reduce the tumours that
I have in my liver and in my lungs.
So it's got a very good chance
of either stabilising the disease
or causing some shrinkage.
And there's about a 50% chance
that it will cause substantial
shrinkage of the tumours,
which would be very good.
That's very good news.
Do you understand about
the side effects?
I understand that they are mainly
connected with skin and that
I mustn't be in the sun too much,
or at all,
and that there can be some rashes.
Probably the other main side effect
is a bit of fatigue.
But not in any serious way.
Yes, yes.
So Rosemary would be bonkers
not to take it?
The answer is yes!
And you're probably going to say
I would say that, wouldn't I?!
But actually, there are treatments
that we give where
we have very long conversations
about whether it's worth it or not.
But I think, in this case,
it's one of those occasions where
we can put our hand on our heart
and say, look,
you really should take it.
And we're going to start today.
Carla has already got the drugs
ready for you. OK?
Yes, that's fine. They are the drugs.
Lovely, fine...
This revolutionary drug fights
cancer in a new and powerful way.
It's one of the new generation of
drugs that have been made possible
by a vast improvement in
our understanding of what cancer is.
Cancer occurs when our cells
divide out of control
and develop the potential to become
immortal.
This happens because the DNA,
the genes at the very heart
of the cell, have gone wrong.
It's Professor Naz Rahman's job to
hunt down those defective genes.
BEEPING
We get DNA,
from individuals who've had cancer,
and then we sequence that genetic
code, and then we compare that
with similar data from people who are
well, who haven't had cancer,
so we can look to
see what the differences are there.
So that we can try to identify
what may be the causative genes
that have led to
that person developing cancer.
In some cases,
faulty genes are inherited,
and can increase
the likelihood of getting cancer.
But less than 10% of cancers are
caused by inheriting faulty genes.
The majority of cancers are not due
to something that's been inherited,
they're due to genetic changes
that have
happened during life in a particular
set of cells that then start
growing uncontrollably
and become a cancer.
These types of genetic faults can
happen to any of us, at any time.
There are certain things
that increase
the likelihood of that kind
of damage occurring, for example,
UV light can make that happen
more likely, the carcinogens in smoke
also lead to DNA being damaged.
In fact, just as we get older,
we gradually accumulate more changes
in our DNA and that's part of
the reason why you are more likely
to get cancer as you get older.
Naz's team is part of a worldwide
network of genetic scientists,
carefully decoding our DNA.
Looking for a fault among the six
billion letters in the human genome
is like looking for
a needle in a haystack.
But finding one is crucial to
developing
a genetically targeted drug.
You get a sense that
when you're making that discovery,
just at that moment at least,
you're the first person that knows
that that gene has caused
that disease, and also you have
an insight into the hope that
that's going to be useful
down the line in terms of helping
patients getting better treatments.
Discoveries like these have
triggered
a revolution in cancer treatment.
The promise that, one day,
if we are struck down by cancer,
keeping it at bay could be as simple
as taking some pills.
The process of hunting for genes has
led to the new melanoma drug
they've been trialling
at the Royal Marsden.
The question now is whether
these innovative new treatments
will deliver the results
they are hoping for.
WHIRRING
After six weeks,
the radiotherapy team have completed
the installation of their robot.
And Dr Nick Van As has begun to
look for suitable first patients.
..50, 55 minutes...
Ray Dean has come to find out
whether he may be eligible
for the treatment.
I don't know whether or not
it's going to be suitable for me
until I see the consultant.
As I say, hopefully they're going
to be able to do it
and, hopefully, that's going to
give me a bit of extra life.
Ray's cancer has spread to
a lymph node.
Unfortunately, it is not operable,
and he has already had the maximum
amount of standard radiotherapy.
But now there is a chance that
the new technique could offer
a crucial lifeline.
Mr Raymond Dean?
It all depends on
Ray's latest scan results.
If the cancer has spread
beyond the lymph node,
it will be too late for
the treatment to go ahead.
Hi, have a seat, nice to see you
again. So, you've had the scan.
Do you want to just go over
the rationale for doing the scan,
do you understand why we did it?
Yes, basically to see
if it was just in the one place.
Yes, OK, so...
And is it just in the one place?
It is. Oh, thank God for that!
That's the first bit of good news.
It's been a really informative scan.
I'll show you the pictures.
That node that we saw on the CT is
this little orange blob that
lights up.
But what we wanted to see was,
did it light up, because if it did
it's very highly suggestive
that that is prostate cancer,
and the other thing is that nothing
else lit up, and nothing else has.
This lymph node is very close to
the area we irradiated before
and that's why we weren't
particularly keen on giving you
standard radiotherapy again.
But I think we can do this,
we can give that a very high dose,
using the CyberKnife, and really
minimise the dose elsewhere.
But there's not no risk, I'm afraid.
Oh, yeah.
I think the risk we can make is
relatively low, but there is a risk.
Yes. But I think it's worth doing.
Definitely.
For Ray and his wife, Janet, it's
an end to weeks of anxious waiting.
'I'm lost for words, really.'
Yes, you know. You come up here very
hopeful that everything's going to
come out right,
and, you know, this CyberKnife has
come along at just the right time.
Six months ago, I wouldn't
have been offered the treatment.
It's good news for us.
Despite it all glowing up there.
And you know, I told you
I'd glow in the dark. Yes!
But...
Well, we've got a few more years to
do caravanning, haven't we?
Well, that's right, yes,
I mean to say, yeah,
absolutely overjoyed, brilliant.
Following his scan results,
the team have decided Ray will be
their very first patient.
And for Nick, the reality of what
they're about to do
is beginning to sink in.
Now that I'm talking to
real patients about treating on
the CyberKnife,
I must say for the first time in
the whole process, I've got nervous,
so now I realise that we're going to
be doing something we've
not done before,
and this is for real.
I'm confident we can do this,
and we can do it safely,
but I will be quite relieved when
the first treatments are behind us.
MURMUR OF CONVERSATION
You have to set a VOI,
but you can set a very broad...
Nick must now start to design
a unique treatment plan
specifically for Ray.
To do this,
he calls on a team of experts.
As well as the doctors
and radiographers,
there are full-time physicists
whose job it is to work out
exactly how the robot will move
around Ray to deliver the radiation.
We're going to force the target dose
into the shell, aren't we?
Yeah, you need... You can't
mix and match structures.
Right now we have no idea what
is the right steps to follow.
So the role of defining the areas
we want to and don't want to treat
is the doctors', and the physicists
then create the plan for us.
The workhorses and the brains.
That's nice!
Which way round was that, Nick?
THEY ALL LAUGH
The physicists are the brains here!
Because the level of radiation
is so much higher
than they would usually
give a patient like Ray,
their plan must be
extremely precise.
If they get it wrong, it could cause
serious damage to Ray's body.
Using scans of Ray's abdomen,
the doctors create a 3D model to see
where to avoid and where to target.
As the plan takes shape,
it's possible to see clearly
what makes this type
of treatment different.
What we're looking at now
is the radiation plan.
These lines represent the angles
or the number of beams
that are coming in
in order to create the dose.
As opposed to a normal plan,
which we just have dose
just coming in from maybe the sides
and one from the front,
you can see that there's loads,
hundreds of lines going in.
By splitting the overall radiation
into individual beams,
delivered from different angles,
each beam only delivers a low dose,
causing less damage
to healthy tissue.
This approach to radiotherapy
has huge potential advantages.
So if you just use three beams,
you've got to put about 30%,
33% of the dose from each beam.
If you're using 100 beams,
you're only going to put 1%
of the dose, theoretically,
so you put a very little amount
of dose through each beam
but the centre is hot.
Radiation is concentrated
on the target
and falls quickly away either side.
At a centimetre distance, the dose
is just 10% of the full amount.
If we did this with standard
radiotherapy, we'd still be
at 50-60% of the dose in that region,
possibly even higher.
So we want this very rapid
fall-off of dose,
and that's what we've achieved
by using all these beams
converging on one target.
In less than 24 hours
this plan will become reality,
as Ray becomes the hospital's
first patient
to be treated with the robot.
You realise there's a lot
of responsibility now
to make sure this goes right.
I wouldn't say I'm stressed about it,
but I want tomorrow to come
and tomorrow to go!
But we'll get there, you know.
Today's about making sure
the plans are correct,
and we'll probably be here
quite late into the evening.
For Phil, the waiting is over.
He's travelling into the hospital
for his operation
on the da Vinci surgical robot.
Goodbye, house. Next time I see you
I'll be without a prostate.
If it goes well,
he could be cancer-free.
'It's almost like you feel
you're going round with a label.
'There's this burden,
there's this tag on you saying,
'"This is Phil
and he's got cancer."
'So I want to get to a point
where I can go round
'and think to myself,
"No, I'm Phil without cancer,"
'and just move on.'
All right? I'll need that!
Put your bag down there and make
yourself comfortable. OK. Thank you.
Before the robot
can be put in place,
the surgical team need
to make preparations
to insert the instruments
and inflate Phil's abdomen
with carbon dioxide
to create space
for the robot to work.
The robot can now be brought in
to replace Chris Ogden
at the operating table.
That's good.
Make sure we don't clash the arms.
Great.
Great.
That's just placing
the instruments inside the patient,
and...the robot's engaged.
Across the room, Chris takes
his position at the console...
Thank you.
..and the operation can begin.
The mechanical movements of
his hands are scaled by the robot,
then translated into precise
micro-movements of the instruments
inside the patient.
He can switch between
three instrument arms
and operate the camera
with a foot pedal.
The camera arm contains
two high definition cameras,
which together give a 3D view,
enabling Chris to get
a sense of depth and perspective.
You start to feel you really are
inside the space,
which is an amazing feeling, really,
because that's exactly
where you want to be as a surgeon -
right in where the action is.
You become part of it
and it becomes part of you.
Prostate surgery is particularly
difficult because all of the cancer
must be removed without damaging any
of the close-lying nerves or organs.
Any complications could leave
the patient impotent or incontinent.
The precision of the robot
promises to reduce these risks.
So now we take this, which is
the prostate. That goes into a bag,
which we'll retrieve
when we remove the instruments.
Just like obstetrics.
And there's our prostate.
The operation is over
and Phil is taken to recovery.
When patients have their prostate
removed with open surgery,
they can expect to stay
in hospital for up to a week.
But because this procedure
is less invasive,
Phil is discharged
in less than 24 hours.
In three months' time,
tests will reveal
what effect the operation has had.
For some people, even the very best
surgery is not an option.
Rosemary Reid is one of
the first patients to be given
a ground-breaking new drug
for melanoma.
She hopes it will extend her life.
We're very lucky
that we're part of the trial
and we're hoping that it will improve
things, and that we will be...
or that I will be one of
the lucky ones that it works for.
Rosemary had two bouts
of chemotherapy
and they didn't work,
so now we've got some hope.
Yep. So...
We'll take it from here
and hope that it will work.
Many of the new treatments being
pioneered at the Royal Marsden
evolved out of work done here,
at the Institute of Cancer Research.
The drug that Rosemary is taking
was the result of an international
collaboration of scientists
and close to
£1 billion of investment.
It began with the hunt for a gene
that drives melanoma.
After looking at hundreds of samples
from melanoma patients,
geneticists made a major discovery.
They found that one gene was mutated
in about half of the patients,
but was normal in healthy people.
It was a gene called BRAF.
About half of the melanomas will have
that specific change in BRAF.
If you look at the DNA
in normal individuals,
you will almost never see
that change.
So what that's telling you
is that that isn't chance.
That there is a specific causal
relationship, is what we call it.
That change in that gene
is critically important
for why those cells
have become melanoma cancers.
People with melanoma are far more
likely to have the mutated BRAF gene
than healthy people, and scientists
here played a key part
in turning this knowledge
into a treatment.
We have the green China tea,
very nice.
Jasmine with flowers. That's very
nice, that smells nice, actually.
Darjeeling, rooibos,
Earl Grey and Ceylon.
(I don't like Earl Grey.)
When Naz's colleague,
Professor Richard Marais,
heard about the mutation,
he knew it was a major find.
When I heard that BRAF was
mutated in half of human melanomas,
I was beside myself with excitement,
because that really tells you
that here,
probably for the first time,
we're starting to understand the
processes that drive the formation
of this one type of cancer.
I think it's very difficult to try
and convey how exciting that was.
His day-to-day work involved
studying normal cell division,
and he suspected the BRAF gene
was involved in that process.
If the BRAF gene was mutated,
he thought that might cause
the cell division to go wrong,
triggering cancer.
To test his theory,
he removed the mutated BRAF
from some melanoma cells in his lab
and amazingly, the cancer cells
stopped dividing and died.
That tells you then that
this is not just a silent passenger
that's not doing anything
in the cancer.
It tells you that
it's what's driving the cancer.
It really speaks to you
and says, "This is where
you should be putting your effort."
He began to examine
the damaged BRAF gene further.
The normal BRAF gene
produces a protein
which activates cell division.
And it is this protein
that's critically important
in the cancer cells.
This is actually the shape
of the BRAF protein,
and what you can see is that
it's got lots of lumps and bumps,
but the most important part
of the molecule is this, here.
You can see this very deep cleft
that really runs into
the heart of the protein,
and that's the business end
of the molecule.
In the normal BRAF protein,
this cleft is closed off
unless the cell needs to divide.
Now, the problem with the mutant
form of BRAF, what we discovered
is that the gate won't close, so the
protein remains active all the time.
I think I can actually illustrate it
using this tea caddy here.
You see that it's got
this nice catch on it.
If we imagine that this is
the BRAF protein,
this is the cleft on the inside,
and by locking the tea caddy,
we can turn the protein off
and keep it off.
But when this catch is broken,
the protein stays open all the time.
It's constantly active
and constantly driving
the growth of the cancer cells.
So then we need to develop drugs
to stop that protein from working.
We can use these tea bags
to illustrate the drug
and the idea is that if we put
enough of these tea bags in here,
we'll block up the cleft and that'll
stop the protein from working
and that means that the cells
won't be forced to proliferate.
Lipophilic pocket, which is...
The next step in developing
any genetically targeted drug
is for the drug designers
to find a chemical which can block
the cavity in the crucial protein.
For Professor Paul Workman,
designing a drug
can be a problem of geometry,
and it is being transformed
by the latest 3D technology.
So what we're looking at here
is the surface of the protein,
a small part of it - the bigger
protein surface is all around here.
In this cavity is the essential
part of this molecule
that makes it cause cancer.
With the target identified,
Paul and his team screen
over 100,000 chemicals,
to see if any show signs
of binding into the cavity.
When they find one with potential,
they turn it into a virtual model.
Here you can see it fills
quite a bit of the cavity,
but not as much as we would like.
It did actually have some anti-cancer
activity, albeit quite weakly, and we
needed to make it more effective.
Using the 3D model,
the team can fine-tune the drug,
atom by atom,
to perfectly fit the entire cavity.
So here you can see the structure
of the much more advanced compound.
You can see it's a more complex
structure, it's bigger,
there's more complexity in geometry,
and as a result
it binds much more effectively.
This drug was 1,000 times
more effective on the cancer cells
than the original hit.
This 3D technology makes
the development of a drug
faster and more efficient
than can be achieved
in the lab alone.
There's a beauty to this
which is absolutely captivating.
I continue to be delighted by seeing
the beauty of the interaction.
Finally, you've got
the best satisfaction,
which is that patients
will benefit from that science.
It's hard to beat.
HE LAUGHS
As more and more genes responsible
for driving cancer are discovered,
scientists will be able to design
increasing numbers
of targeted drugs.
The ambition is that in the future,
there will be drugs
to act on every type of cancer.
There's a picture of the day.
Now, I can't find one.
It's the morning of Ray Dean's first
robotic radiotherapy session
and the start of a treatment,
which he hopes will extend his life.
Some of it is just the waiting,
going back to the old days,
when you're playing football,
tension all builds up inside you.
Once you get on the pitch there,
completely different. It just goes.
Once you're out there,
then it's all gone.
So I suppose, you know,
this is the same thing.
FAINT BEEPING
For the last two days,
the radiotherapy team have been
running final tests.
Not everything has gone smoothly.
You'll have to come round
and let him in.
Hugh, this...
This is a whole series
of error messages that's trying to,
we're just trying to turn it all off
and reboot it and start again,
which is very frustrating.
I think it's got stage-fright
this morning. I know.
Even a machine this sophisticated
sometimes needs switching off
and on again.
WHIRRING
The pressure must be on everybody
involved at the Marsden,
as well as myself and, um...
let's hope everything goes well.
A, B and C...
I'll go and find the case. OK.
Just sorting out the music.
After years of planning
and months of preparation,
this robot is about to deliver
radiation to a patient
for the very first time.
Put your hand up if you need to say
anything, we'll come through.
Cheers. Thank you.
CONTINUOUS BEEPING
Is that everybody?
OK, so we'll see
you at the end.
Mmm. About an hour,
we'll see you then.
For the next 45 minutes,
the robot delivers the highest
dose of radiation
they've ever given a patient
like Ray.
Because of this, his treatment
will take only three sessions.
A dramatic improvement on the 35
sessions of radiotherapy
he had before.
In four weeks' time,
a blood test will reveal
if the treatment has begun
to take effect.
Phil Garrard is back out
running with his sons,
three months after his operation
with the surgical robot.
He has been given the results
of his blood test,
which will reveal if his prostate
cancer is still there.
They said the result
was unrecordable,
which is what I think everybody's
looking for.
It wasn't even on the scale.
So the lower it is, the better,
but mine was unrecordable,
because it was so low.
You get confidence that they've
cracked this horrible disease
and it's not a thing to be
so fearful as it used to be.
The development of robotic surgery
is promising to increase precision
and dramatically reduce recovery
times for patients of the future.
Two months ago,
Ray Dean was hoping a new form
of radiotherapy
would extend his life.
He's now here for the results
of his PSA blood test,
a measure of the level of cancer
that remains.
Well, the good news...
The good news?
It's worked well.
The PSA has
fallen from 21 to 5.6. So..
That's absolutely amazing.
We couldn't have wished for better
news. No, it's great, I'm delighted.
I have to be honest,
I was quite nervous...
LAUGHTER
Yes, yeah, yeah. So, very relieved.
As I said to you,
it's probably earlier I normally
would be checking it,
although there isn't really
a normal for us in this. No, no.
So, but I mean, that's, I hope
that it will continue to fall. Yes.
So to be so much lower
in such a short period of time,
it's exactly what we wanted to see.
Yes. That's absolutely brilliant.
Over the moon. Over the moon.
I had every confidence,
but it's nice to actually hear
that it has worked.
Yeah. And so well.
The good thing is there that,
as the doctor said, you know,
I'm the first one and, you know,
they're hoping for a good result,
which is what they've got, and I mean
to say, I've got a good result.
So, it's celebrations time.
LAUGHS
It's great to have the very
first patient we treated
with a good outcome.
As I said, it's very early days,
but it's great to have a good
outcome on number one.
The fact that it's had such a
significant fall,
you know, suggests the decision we
made to do it was the right one
and the fact that
he's almost more pleasingly,
he's had no problem
with the treatment.
He's perfectly well and he's
continuing to work full time
and it hasn't really appeared
to impact his quality of life
at all.
For Nick, this is just the
beginning.
He is comparing the procedure
to standard radiotherapy
in a series of trials,
and plans to start treating
a wider range of cancers.
Two months after starting
on the genetically-targeted drug,
Rosemary Reid is back for her scan,
to see if it has had any effect.
'Scans are always little
peaks in one's treatment
'and it's scary having the results.'
Can I just get you to confirm
your full name and date of birth?
Unfortunately, after a week
of taking the pills,
Rosemary developed some side effects
and had to have a temporary
break in her treatment.
Bring your arms right above
your head for me.
'I'm not sure how much
success I'll have,
'because I've had to be off
for three weeks
'because of the rashes I had.'
Breathe normally.
'So, it may not show
to be as effective as I'd hoped.
'It was very, very disappointing
to have to come off it,
'because I thought,
I'm losing time here.
'You know, all this time
the tumour is growing,
'and coming off it was the last
thing I wanted to do.'
It's all finished.
24 hours later,
in the melanoma clinic,
Dr James Larkin
has Rosemary's results.
Hi.
Hello, nice to see you again.
Nice to see you again as well.
Hi.
Thank you. Nice to see you again
as well, sir.
Have a seat, James, please.
So, the scan was good.
Oh, really?
That's the most important thing
of all. Fantastic.
So, definite shrinkage of pretty
much all of the abnormalities
we could see in the liver,
significant shrinkage.
That is fantastic,
as I really didn't think
there would be any change
after the reduction
in the dose.
Oh, really? Yes.
No, no, no. Definitely dramatic
shrinkage, really.
And certainly in the lungs,
some of the abnormalities
have disappeared altogether.
So it's great.
Wow, that's fantastic.
What you can see here is a scan
just before you started treatment,
and then the scan from yesterday.
And these sort of black
areas are the lungs.
For example, there, you see
that sort of spot there,
that's a bit of melanoma in the
lungs before you started treatment
and then there,
I can't really see it at all.
And, in fact, most of the
abnormalities in the lungs
have pretty much disappeared
altogether,
which is obviously great news.
And then if we were to look
at the liver,
which is the other main place that
we know there are abnormalities,
you see the sort of darker
grey areas,
those are the lumps of melanoma
and then if we look at a scan
from afterwards... Good lord.
..you can see there,
it's pretty much half the size.
The other ones have got smaller
as well. Pretty much everything,
everything you look at
is smaller.
So it's wonderful.
That's wonderful news.
So it's nice to be able
to tell you that...
To actually see a reduction
was fantastic. Mm-hm.
Because, it was just like
a surprise.
It was like getting
As for A-level
when you thought you were
going to get all Cs.
It was brilliant,
absolutely wonderful news.
..side effects. Yes, yes...
'Really for the last 20
or 30 years,'
discussing scan results
with patients on treatment,
nine times out of ten,
it would be a conversation
about how the scan is worse
and it's almost the opposite now.
Eight or nine times out of ten
with this treatment,
you can say to the patients,
things have got better
which is a great feeling,
particularly on a background
of so little progress
treating this disease, really,
since the 1970s.
It's given us a lot of time,
yes, I think so. Yes.
Shall we go to Nepal
at the end of October?
We could do, yes.
SHE LAUGHS
Yes, no, it certainly means
we can plan for the future more now
and look forward to things,
and...yeah.
So I shall not give my
winter clothes to Oxfam.
Too right. I shall buy
some new ones. Yeah.
Rosemary will keep taking
the drug for as long as it
continues to work.
It's not yet a complete cure,
but drugs like these,
based on understanding cancer,
offer our greatest hope that one day
we'll be able to defeat
this disease.
We have to be cautious
about all these claims
that the cure is
just around the corner.
Cancer is a remarkably
complicated problem,
but we should understand
that progress is being made.
Understanding exactly
what's causing cancer
means that more
drugs can be created,
with the promise of increased
life expectancy and future cures.
In the next five to ten years,
I think we'll have catalogued
pretty much all of the cancer genes,
we'll have a very good understanding
of exactly how they work
and how they interact with each
other to cause cancer
and develop inhibitors
against the majority of those.
By combining technology
with scientific knowledge,
the future of cancer treatment
looks better for us all.
We are making inroads
at multiple different levels.
So, from a genetic level to a drug
development level,
to accurately delivered radiation,
or surgical techniques,
I think it's a great time to be
working in the field
and I think we'll actually try and
target tumours more scientifically
and give us a much better chance
of eradicating the cancers
than we have done in the past.
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