November 2, 2016

Irish scientists find new hope in overcoming potentially deadly form of breast cancer

Irish scientists have found a potential new way to treat one of the most aggressive and difficult to treat forms of breast cancer.

Researchers from BREAST-PREDICT, an Irish Cancer Society Collaborative Cancer Research Centre, have shown that a new drug – APR-246 – can prevent the growth of triple-negative breast cancer cells. The findings from their work have recently been published in the International Journal of Cancer.

If found to be successful in clinical trials, APR-246 has the potential to save lives for patients with a form of breast cancer which is currently difficult to treat.

More than 250 people are diagnosed with triple-negative breast cancer each year. The subtype accounts for approximately one in six breast cancer cases globally.

Triple-negative breast cancer is often aggressive, difficult to treat and tends to be more common in younger women.

The research was carried out by PhD student Naoise Synnott (pictured), under the supervision of Professor Joe Duffy and Professor John Crown, and was recently published in the International Journal of Cancer.  

It involved laboratory tests in combination with current chemotherapy treatments and was funded by BREAST-PREDICT and the Clinical Cancer Research Trust.

Based in St Vincent’s University Hospital and UCD, the research team now hopes that APR-246 can be tested among patients in clinical trials which, if successful, could lead to the drug being made available for patients with triple-negative breast cancer.

Commenting on the findings, Naoise said:

“At the moment the only form of drug treatment available to patients with triple-negative breast cancer is chemotherapy. While this will work well for some patients, others may find that their cancer cells don’t respond as well as might be hoped to chemo, leading to patients suffering the side effects of this treatment without any of the desired outcomes.

“I decided to focus my BREAST-PREDICT research on triple-negative breast cancer because it was clear that work needed to be done to provide better and more targeted treatment for these patients. I hope that the work of me and my colleagues in St Vincent’s and UCD will be a big step in providing better treatment and hope to future triple-negative breast cancer patients.”

Professor William Gallagher, Director of BREAST-PREDICT, added:

“Over the last two decades, drugs such as Herceptin have been discovered to target or block proteins that are responsible for the growth of some breast cancers.  

“However, finding a similar drug therapy for triple-negative breast cancer has so far alluded scientists, making these findings all the more important. If successful in clinical trials, APR-246 will be shown to have been effective in targeting a gene known as p53, a gene which is altered in almost all cases of triple-negative breast cancer.

“BREAST-PREDICT is proud to have supported Naoise in her work in this area. Since our establishment in 2013, we have grown to a team of more than 50 researchers around the country, all committed to improving our understanding of breast cancer and finding new and better ways to treat the disease.”

The outcome for patients with breast cancer has greatly improved in recent years. Today, survival rates for breast cancer have increased to 85% over five years.

Newer, more personalised treatments have played a huge role in this high survival rate, with drugs such as Herceptin and hormone therapies like Tamoxifen attacking the three important ‘biomarkers’ which are detectable in most strains of the disease in patients - estrogen receptors, progesterone receptors and HER2.

Triple-negative breast cancers lack these targets. While the disease often responds well to older chemotherapy drugs, there are currently limited options in terms of more targeted and less toxic treatments.

A mutation of the p53 gene does, however, occur in around 80% of these triple-negative breast cancers. Naoise and her colleagues have now shown that APR-246 can act by correcting or neutralising the mutant form of p53, thereby stopping the growth of triple-negative breast cancer cells which have been grown in the laboratory.

Head of Research at the Irish Cancer Society, Dr Robert O’Connor, hailed the development as a significant milestone in the ongoing work of BREAST-PREDICT.

“This paper highlights the vital work which the Irish Cancer Society invests in through the generous support of the public. Our research programmes like BREAST-PREDICT and the doctors, nurses and scientists we fund all across Ireland are looking for new advances to overcome cancer through research.

“These research programmes focus on finding new ways to prevent as many cancers as we can, ensuring the most advanced personalised treatment options are available and that as many patients as possible thrive after their treatment. The number of people with cancer in Ireland is expected to double by 2040, and more research is vital if to tackle this growing epidemic of cancer.

“Since 2010 the Irish Cancer Society has invested €20million in vital research. This is all thanks to the Irish public who continue to fund our work. Throughout October communities, clubs, schools and workplaces got behind our ‘Paint it Pink’ campaign which raised vital life-saving funds that will go towards our continued investment in breast cancer research, as well as advocacy and services. We are truly grateful to everyone who took part in the campaign because without people like them, work like Naoise’s may never have come to fruition.”

An abstract of the International Journal of Cancer article: ‘Mutant p53: a novel target for the treatment of patients with triple-negative breast cancer’, by N.C. Synnott et al. can be viewed here.