Nav: Home

Gene test could pinpoint patients sensitive to new type of cancer drug

December 22, 2016

Testing for a gene commonly mutated in ovarian cancers could pick out patients who will respond well to a promising new class of cancer drugs, a major new study reveals.

Scientists found that defects in a gene called ARID1A caused sensitivity to new drugs targeting the DNA repair process within tumour cells.

The new drugs - called ATR inhibitors - are already being tested in early clinical trials, and the new research could help identify those patients who will benefit most.

Scientists at The Institute of Cancer Research, London, used molecular screening techniques to find that cancers with mutations in ARID1A were particularly sensitive to ATR inhibitors.

ARID1A is mutated in a wide range of hard-to-treat tumour types, including ovarian cancer and stomach cancer, but until now there has been no way of targeting treatment at tumours with this genetic defect.

The research, which is published in the journal Nature Communications, was funded by Cancer Research UK and Breast Cancer Now.

Scientists at The Institute of Cancer Research (ICR) found that ATR inhibitors stopped cancer cells with ARID1A mutations from growing, both in culture dishes and in mice.

They also found that switching off the ARID1A gene in breast and bowel cancer cells greatly increased their sensitivity to ATR inhibitors.

The researchers found the treatment killed cancer cells with ARID1A mutations through a process called 'synthetic lethality'.

Cancer cells with ARID1A mutations become particularly reliant on the DNA safeguarding activity of the ATR protein to survive - so they are especially sensitive to drugs that block its effects.

Patients on clinical trials of ATR inhibitors could now start to be tested for ARID1A mutations in their tumours - in order to assess whether those with the genetic defects are particularly likely to benefit.

Dr Chris Lord, Leader of the Gene Function Team at The Institute of Cancer Research, London, said: "Our research has opened up a potential way of personalising treatment for cancer by targeting drugs to those patients who will benefit most.

"We found in cell cultures and in mice that cancers with defective versions of the ARID1A gene are particularly sensitive to a new class of drug called ATR inhibitors."

"Our research could lead to patients with ARID1A mutant tumours being assessed for whether they respond particularly well to this new class of cancer treatment."

Dr Justine Alford, Cancer Research UK's senior science information officer, said: "By identifying a potential way to exploit a specific genetic vulnerability in cancer this research could point the way to tailoring treatments to each patient, helping to make them kinder and more effective. The next steps will be to better understand the effects of targeting this weakness, and to find out whether this promising strategy will work in people."

Katie Goates, Senior Research Communications Officer at Breast Cancer Now, said: "This early finding could bring us a step closer to more 'personalised' medicine, targeting treatment to exploit weaknesses in patients' tumours and hopefully improve their chances of survival.

"It's particularly exciting to see an idea that was initially tested in breast cancer cells be translated into potential benefit for a number of other cancers. We hope these findings now lay the groundwork for clinical trials to investigate the potential of ATR inhibitors as a targeted cancer treatment in the near future."
-end-
For more information please contact Claire Hastings on 020 7153 5380 / chastings@icr.ac.uk. For enquiries out of hours, please call 07595963613

Notes to editors

The Institute of Cancer Research, London, is one of the world's most influential cancer research organisations.

Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four centres for cancer research and treatment globally.

The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it is a world leader at identifying cancer-related genes and discovering new targeted drugs for personalised cancer treatment.

A college of the University of London, the ICR is the UK's top-ranked academic institution for research quality, and provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.

The ICR's mission is to make the discoveries that defeat cancer. For more information visit http://www.icr.ac.uk

Institute of Cancer Research

Related Breast Cancer Articles:

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.
Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.
More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.
Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.
Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.
More Breast Cancer News and Breast Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...