Defeating Cancer Horizon

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.

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