Researchers from the Institute of Cancer Research (ICR) have found a way to predict how long prostate cancer patients will respond to the PARP inhibitor olaparib.
The research published in the journal Cancer Cell could help doctors personalise treatments and pave the way for the development of new drugs that prevent resistance.
Prostate cancer is the second most common cancer in men globally, with more than 52,000 cases of the disease diagnosed in the UK every year.
AstraZeneca and Merck & Co’s – known as MSD outside the US and Canada – olaparib already holds approvals to treat certain cases of prostate cancer under the brand name Lynparza.
PARP inhibitors such as olaparib work by stopping cancer cells from repairing their DNA and have significantly changed treatment for advanced prostate cancer in recent years, but the length of time that patients respond to them varies.
Funded by AstraZeneca, Prostate Cancer UK, Movember, Cancer Research UK and Prostate Cancer Foundation, the researchers analysed blood samples from 25 patients with advanced prostate cancer who took part in the phase 2 TOPARP-B trial and had all initially responded well to olaparib.
They were able to see that patients with a high number of certain DNA changes called reversion mutations had an average survival time of 13.9 months, compared to 21.4 months for those with a lower number of these changes.
Reversion mutations work by restoring function back to the already mutated genes and, according to the ICR, this is the first research to study the link between them and clinical outcomes for prostate cancer patients.
Kristian Helin, chief executive of the ICR, said: “Drug resistance is one of the biggest problems we face in treating cancer. Knowing which cancers will develop resistance in advance means that we can move patients onto alternative treatments, or new combinations of treatments, to keep their cancer at bay for longer.
“This study gives us an insight into how this resistance to PARP inhibitors – such as olaparib – develops, and I look forward to seeing future research into targeting this mechanism.”
The findings come just two months after ICR researchers found that prostate cancer patients with high levels of a specific protein have significantly poorer outcomes compared to those without.
The findings published in the Journal of Clinical Investigation suggest that BCL2, a protein responsible for preventing cell death, could be a new drug target for the disease and be used to help predict which patients will become resistant to hormone therapy.