New research carried out by Medical Research Council (MRC) scientists shows that cancer can develop in people born with one defective copy of the BRCA2 gene even when the second copy is still working effectively in cancer cells. By studying the development of pancreatic cancer, this discovery not only signals an entirely new approach to studying the origins of cancers associated with BRCA2, but could also help to improve treatment options for patients who are resistant to a group of drugs currently under development, known as PARP inhibitors.

The body’s cells contain many ‘tumour suppressor’ genes whose job it is to prevent cancer. Each cell contains two copies of the tumour suppressor gene BRCA2 and this discovery challenges the long-held view among cancer researchers that both copies of this gene must be turned off in order for cancer to develop.

The team at the MRC Cancer Cell Unit, led by Professor Ashok Venkitaraman, has shown using studies in the laboratory and in patients that even one damaged copy of BRCA2 is enough to cause pancreatic cancer, and the second copy need not be damaged. By discounting the idea that both BRCA2 copies must be damaged for cancer to occur, this work could have wide-reaching implications for studying the origins of other cancers associated with the faulty gene.

The new research may also help to explain why some patients are resistant to a new class of drugs currently under development called PARP inhibitors, designed to kill only tumour cells in which both copies of BRCA2 have been damaged, without harming other cells. PARP inhibitors are a group of potential life-saving treatments currently under development for patients who develop inherited cancers of the breast, ovary, prostate or pancreas.

The study, published in the journal Cancer Cell, suggests that not all patients may respond to the new drugs and that screening would be needed to allow clinicians to prescribe the most effective treatments.

First author, Dr Ferdinandos Skoulidis at the MRC Cancer Cell Unit, says: “Our work shows for the first time that a single defective copy of BRCA2 can promote the development of pancreatic cancer without the need for inactivation of the second copy. the study also highlights that when both BRCA2 copies are damaged, patients may develop a different form of the disease than in cases where only one copy has stopped working.”

Team leader Professor Ashok Venkitaraman, director of the MRC Cancer Cell Unit, adds: “This research challenges existing beliefs about the role that BRCA2 plays in the origin of inherited cancer. We hope that these findings will help clinicians to select the patients most likely to benefit from new drug treatments such as PARP inhibitors, particularly in the case of pancreatic cancer.”

Around twenty-one people are diagnosed with pancreatic cancer in the UK every day. Patients often have few symptoms, meaning that it is difficult to diagnose until it is at an advanced stage. Once diagnosed, fewer than one in five people will survive for more than a year, and only around three per cent will survive for five or more years. Familial pancreatic cancer accounts for up to 10 per cent of patients with the disease.

Research into the genetics and biological indicators that underpin different predispositions for disease is a crucial part of the Medical Research Council’s strategy. a greater understanding of our predisposition to disease will help to tailor future treatments for different diseases and patients.

Contact: The MRC Press Office, Tel: +44 207 637 6011, Email: ac.uk

Source: Medical Research Council (MRC)