Precision medicine for prostate cancer takes a step closer. Researchers have created a three-in-one blood test they say can predict a patient’s response to PARP inhibitors, as well as how well the drugs may impact survival, and how likely patients are to develop drug resistance.
Study co-author Prof. Johann de Bono – of The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, both in the United Kingdom – and colleagues recently reported their findings in the journal Cancer Discovery.
According to the American Cancer Society, around 161,360 new cases of prostate cancer will be diagnosed in the U.S. this year, and more than 26,000 men will die from the disease.
Inherited gene mutations account for around 5-10 percent of prostate cancer cases. A small number of inherited cases are caused by mutations in genes that normally help to repair damage to a cell’s DNA, such as BRCA1 and BRCA2 genes.
For patients with advanced prostate cancer caused by these gene mutations, research has shown that a class of medications called PARP inhibitors is effective for killing prostate cancer cells.
Prof. de Bono and team note that while some patients respond well to these medications, others stop responding early on or develop resistance to the drug. Their new study, however, may lead to better identification of which prostate cancer patients are likely to respond to PARP inhibitors.
The researchers analyzed the levels of cancer DNA that were circulating in the blood of 49 men with advanced prostate cancer, of whom 16 responded to treatment with a PARP inhibitor called olaparib.
Among men who responded to the drug, the team identified a median 49.6 percent drop in circulating cancer DNA after 8 weeks of treatment. However, men who did not respond to olaparib showed a median increase in circulating cancer DNA of 2.1 percent after 8 weeks of treatment.
This finding indicates that levels of circulating cancer DNA could help doctors to pinpoint which patients are most likely to respond to PARP inhibitors. If response rates appear low, patients could be switched to an alternative treatment in a matter of weeks.
The researchers found that they could also identify patient survival as a result of olaparib treatment. Compared with men whose circulating cancer DNA remained high after 8 weeks of olaparib treatment, those with reduced circulating cancer DNA lived an average of 7 months longer.
Finally, the researchers identified biomarkers that could help predict a patient’s likelihood of developing resistance to olaparib. Among patients who stopped responding to the drug, the researchers found that their cancer cells had acquired genetic changes that counteract the DNA repair mutations that first made them vulnerable to olaparib.
While the novel blood test requires further testing in a larger group of patients, researchers believe that it could pave the way for a “new era of precision medicine for prostate cancer.”
“From these findings, we were able to develop a powerful, three-in-one test that could in future be used to help doctors select treatment, check whether it is working and monitor the cancer in the longer term,” says Prof. de Bono.
“We think it could be used to make clinical decisions about whether a PARP inhibitor is working within as little as 4 to 8 weeks of starting therapy.”
Prof. Johann de Bono
“Not only could the test have a major impact on treatment of prostate cancer, but it could also be adapted to open up the possibility of precision medicine to patients with other types of cancer as well,” he adds.