Within sight: the end of breast cancer

[Guest guest]

http://www.timesonline.co.uk/tol/life_and_style/health/article7095652.ece

The most common cancer could cease to be a killer within ten years, say

scientists

I'm looking down a powerful microscope at breast cancer cells, a little cluster

of them multiplying all by themselves in a nutritious pink culturing fluid. You

can barely see them unless you're told what to look for - they're insignificant,

irregular, too chaotic to make a person die. But they do: 12,000 each year in

the UK.

 

Around me in Breakthrough Breast Cancer's research centre in London, the walls,

the coats, the work units are all white, as you'd expect in one of the world's

leading cancer labs. But it's surprisingly cramped, untidy and a little stuffy.

There's The Verve playing on the radio, journal print-outs spread across tables,

and the scientists - sitting at benches framed by rows of pipettes and

blue-topped bottles - look frighteningly young. Over the next ten years, with a

bit of luck, they and their successors will make breast cancer a condition from

which you don't die any more.

 

They work at the UK's only dedicated breast cancer research centre, which, in

the 12 years since it was established, has put eight new treatments into

clinical trials. In 2005 it was responsible for arguably the biggest cancer

breakthrough in a decade - the discovery of a new class of cancer drugs called

PARP inhibitors (see below).

 

What next? The scientists are putting together an armoury of targeted weapons

against breast cancer. But, contrary to expectations, they're not pursuing a

" magic bullet " cure - researchers now know that breast cancer is not one disease

but many, each with its own vulnerabilities. They're finding many different

lines of attack to give doctors options whatever direction a cancer takes. And

they're making real progress.

 

" We're learning that you need to know how to hit cancers on many fronts because

all treatments can result in resistance or relapse, " says Professor Clare

Isacke, deputy director of the centre and a molecular cell biologist. " There are

also lots of aggressive cancers for which we have no targeted therapies, but

they are starting to be picked off one by one as we find new targets. By

understanding the tumour biology better you can find new targets. "

Breakthrough has assembled specialists in all areas of breast cancer -

oncologists, geneticists, cell biologists and drug experts - at its centre at

the Institute of Cancer Research, with which it is partnered. There are 120

senior scientists, PhD students and post-doctoral researchers from Italy, Spain,

Iran, Bulgaria and Germany as well as the UK - all banging their heads together,

going to the pub together, coming up with ideas, experiments and findings that

have real clinical relevance for women with breast cancer. Many work closely

with the neighbouring Royal Marsden Hospital.

 

They spend weeks, months, years even, on experiments that are looking for ways

that cancer cells differ from " normal " cells - in structure, genetics and

behaviour. Once understood, these distinguishing characteristics can provide a

way in for treatments - allowing drugs to disrupt the welfare and growth of

cancer cells, but not normal cells.

 

Nicole Simonavicius, a 30-year-old PhD student from Germany, has spent four

years trying to find a source of weakness in the blood vessels that breast

tumours create around themselves to provide nutrients. She has confirmed that

cancer-created blood vessels contain a substance called endosialin, which normal

blood vessels do not. She has pinpointed for the first time the type of cell in

blood vessels that produce the endosialin: support cells called pericytes. And

she thinks she knows why endosialin is vital to the formation of tumour blood

vessels.

 

This is potentially very exciting: a drug targeting endosialin could prevent a

tumour from forming blood vessels, causing it to starve. What's more,

Simonavicius believes that she has uncovered vital information about how

endosialin affects blood vessel formation, which may lead to new drug

treatments.

 

She is clearly excited at what she has found but she sees the potential

significance of her work only in occasional glimmers. " I never see cancer as a

disease that kills people. I see it as my work. It's only when women who

fundraise come to visit that I get a bigger picture. "

 

Simonavicius used confocal microscopy - an imaging technique - to identify where

the endosialin was; she found it delicately wrapped round the outside like a

ribbon. Her eureka moment came when she was comparing blood vessels formed by

cancer cells, which could produce endosialin, with normal blood vessels that

could not. Looking at the cultures, she knew something was different. " Somehow

the ones with endosialin looked more messy. " A colleague suggested that she run

a computer analysis of the images, and the data confirmed not only a difference,

but a pattern to that difference. The full details of her findings are under

wraps until they are published in a medical journal within the next year.

 

She looks appalled when I suggest that there is an element of drudgery to the

work. " I don't find it at all repetitive, " she says. " You wait for an outcome to

your experiments, and that always poses another question you want to answer. "

 

At the stool next to Simonavicius is Dr Nirupa Murugaesu, a breast oncologist at

St Bartholomew's Hospital, in central London, who is at present involved in

research. She is trying to find clues about the cellular processes that cause

breast cancer to spread to other parts of the body (metastasis). " As a doctor, I

know that the main problem we have is when breast cancer spreads, and it would

make a huge difference to have more options at that stage, " she says. She is

trying to pinpoint which genes activate metastasis.

 

Finding new targets that manifest themselves only when cancer spreads is a

priority for the centre. Very little is known about these secondary cancers even

though they are the ones that usually kill people. This is partly because

doctors rarely take tissue samples because, unlike primary breast cancers, they

tend to be too difficult to remove. As a result their cell biology has not been

closely studied.

 

Murugaesu grows cancer cells in culture, then, by adding another type of genetic

material called RNA, she " silences " certain areas of genetic coding (genes) so

that she can observe the effect of the remaining genes. " What I'm doing is not

yet close to a clinical application, " she says, " but it will hopefully show

which genes are important, and which ones increase sensitivity to certain drugs.

I find it inspiring that, during my working lifetime, we could have improved the

treatment of secondary breast cancer so much that it has become, like diabetes

or high blood pressure, a condition you manage with medications for life. "

 

Clare Isacke says that she feels a sense of responsibility to use the funds

raised by the public effectively. She will be one of 15 high-achieving women -

Booby Birds, as they've been dubbed - who will be throwing themselves out of an

airplane next month, each trying to raise £20,000 for Breakthrough and the

cancer lab she helps to run. " But it does happen sometimes that an experiment is

badly planned, or simply doesn't work, and that's part of the learning process. "

 

But is it right that the breast cancer research agenda attracts a pink blanket

of press coverage with glamorous figureheads such as Kylie Minogue, Claudia

Schiffer and now Martina Navratilova, while the fundraising efforts for

prostate, bowel and lung cancer get squeezed out? She acknowledges a problem.

" If this amount of money had been spent on lung cancer, which is almost as

common, we'd have made much more progress there, " she says.

 

But she reels off the reasons why breast cancer research deserves every penny it

gets: breast cancer is the commonest cancer; there are more tissue samples to

analyse than for other cancers; knowledge gained often benefits other cancers;

the amount of money it gets is proportionate to its incidence.

 

It's reasonable to predict, she believes, that through the work of this centre

and others around the world, breast cancer will cease to be a killer in little

more than a decade. " There isn't going to be one wonder drug. But we will be

giving women cocktails of drugs to weaken the cancer in multiple ways. In an

ideal world, we'd prevent or cure breast cancer, but living with it as a chronic

disease is considerably better than dying of it. "

 

 

The science behind the drugs

 

Breast cancers caused by a mutation on genes called BRCA1 or BRCA2 have proved

hard to treat. But researchers at Breakthrough have discovered that the DNA of

the mutated cells, unlike that in healthy cells, depends for its welfare on a

protein called PARP. Drugs that block PARP make the cells die. These drugs are

being trialled and are unlikely to be available for at least two years, but

there is already some evidence that they will help cancers caused by other gene

mutations too.