KuDOS Pharmaceuticals: Breast Cancer Breakthrough Excites Scientists
04/14/2005
Breast Cancer Breakthrough Excites Scientists
By Steve Connor, Science Editor, The Independent (United Kingdom)
14 April 2005
A drug that can destroy tumours with minimal side-effects could offer a
breakthrough in the treatment of breast cancer.
Tests on animals have shown the drug prevents the growth of tumours so
effectively that clinical trials on humans will start within months, scientists
said yesterday.
The drug is called a PARP inhibitor and is targeted to work against tumours
caused by the inherited forms of breast cancer which result from mutations in
the BRCA1 and BRCA2 genes.
Women carrying mutations in either of those genes have up to an 85 per cent
chance of developing breast cancer by the age of 70. There is no specific
treatment other than a prophylactic mastectomy.
Nearly 41,000 British women are diagnosed each year with breast cancer and,
of those, about 5 per cent have strong hereditary factors, such as mutations in
one of the two BRCA genes.
However, the new drug might also be effective against other non-hereditary
forms of breast cancer and could end up helping as many as 20 per cent of breast
cancer patients, said Professor Alan Ashworth, director of the Breakthrough
Research Centre at the Institute of Cancer Research in London.
"This is a brand new therapeutic approach, centred on exploiting a specific
deficiency in breast cancer cells - their Achilles' heel. This is only possible
because of our ever-increasing understanding of the basic molecular biology of
cancer," Professor Ashworth said.
Mutations in the breast cancer genes cause cells to proliferate
uncontrollably and cause a tumour. The new drug induces another change in these
cells that prevents them from repairing any further damage to their DNA, causing
chromosomes to fall apart and the cancer cells to die.
"It's analogous to removing two legs of a table. Removing one leg is damaging
but removing two causes the table to fall over. That is what the drug does to
the tumour cell," Professor Ashworth said.
Most patients with breast cancer are treated with drugs that destroy cancer
cells but can also damage healthy cells - it can lead to distressing side
effects, such as nausea and loss of hair.
Professor Ashworth said the study on laboratory mice, published in the
journal Nature, indicates the PARP drug is highly selective and appears to
destroy cancer cells only, leaving healthy cells untouched.
"We've made this added leap. We've got a drug that works effectively and it's
going into patients very soon. It real progress and has caused extreme
excitement," he said.
Breast tumours in women who inherit mutations in either of the two BRCA genes
occur because the cancer cells have lost a specific mechanism that can repair
damage to DNA.
PARP inhibitors selectively kill cells where that form of DNA repair is
absent and so are highly effective at destroying cancer cells but leave ordinary
cells unharmed because they still have the vital mechanism for DNA repair.
In laboratory mice with implanted tumour cells, none went on to develop
cancer after treatment with PARP and yet up to 80 per cent of the other
"control" mice that had no treatment developed tumours.
Andrew Tutt, an oncologist at Guy's Hospital in London and a member of the
research team, said: "Targeted treatment holds considerable clinical promise. If
our laboratory findings are confirmed in the clinic, we could dramatically
improve the treatment of patients with BRCA1 and BRCA2 associated cancers.."
The drug was the result of 10 years of research by
scientists working for Kudos, a pharmaceuticals company based in Cambridge.
Professor Steve Jackson, the chief scientist at Kudos, said: "This discovery
could well be the tip of the iceberg, as the technology behind it has the
potential to treat a range of other cancers."
The research was jointly funded between the medical charities Breakthrough
Breast Cancer, Cancer Research UK, the Wellcome Trust and the Mary-Jean Mitchell
Green Foundation.
Case Study: Joan Nicholson, charity consultant
Joan Nicholson, a charity consultant from Middlesex and carrier of the BRCA2
gene, had a full oophorectomy (mastectomy and reconstruction) two years ago and
a hysterectomy six months ago, as preventative measures to protect her from
developing cancer.
"The cancer that runs in my family is a very aggressive form. Seeing members
of my family going through chemotherapy, I felt I needed to do something to
protect myself and I didn't feel there was anything out there other than having
the surgery.
"I was given the option of having cancer tests, but with this strain, once
you've found the cancer it is too late. The worst thing about the surgery was
actually what people said about having my ovaries removed - that I would get
night sweats and depression. Luckily I haven't had any of those symptoms.
"I am very worried about the girls in my family. There are a couple who do
have the gene and others who haven't been tested. If I was younger and in a
position to try the new treatment, it could make a big difference, even if the
drug could just buy some time for sufferers or carriers of this gene.
"Some women I know had testing and know they carry the gene but are going to
go ahead and take their chances.
It is a very hard decision to make. "There are a lot of different kinds of
cancer but for BRCA1 and BRCA2 carriers, this could make a big difference."
Past drugs
The hormonal drug Tamoxifen has been the gold standard in breast cancer
treatment since the 70s. It has cut the death rate from breast cancer by
reducing the recurrence of the disease in women who have had surgery and/or
radiotherapy by 50 per cent. However, side effects include an increased risk of
blood clots, stroke and endometrial cancer.
The development of a new class of drugs called aromatase inhibitors in the
past five years has persuaded many doctors they found a breakthrough. Results
from a trial of the first drug, called anastrozoleshowed it cut the recurrence
of breast cancer in women who had already been treated for the disease by 76 per
cent, with a lot less side-effects. |
