Prostate cancer is the most common cancer among men in the United States after skin cancer. According to the American Cancer Society, about 160,000 new cases of prostate cancer in the United States will be diagnosed this year, and more than 26,000 patients will die from the disease. Hereditary gene mutations account for about 5-10% of prostate cancer cases. A small number of inherited cases are caused by mutations in genes that normally help repair DNA damage to a cell, such as the BRCA1 and BRCA2 genes. For patients with advanced prostate cancer caused by these mutations, research has shown that a class of drugs called PARP inhibitors is effective for killing prostate cancer cells.
But precision medicine takes another step forward. The researchers created a three-in-one blood test that says they can predict a patient’s response to PARP inhibitors, as well as how medications can affect survival and how patients can develop drug resistance. The co-author of the study, prof. Johann de Bono, from the Cancer Research Institute and the Royal Marsden NHS Foundation Trust, both in the UK, and his team of researchers recently reported their findings in the journal Cancer Discovery. The professor De Bono and the team observe that while some patients respond well to these drugs, others stop responding promptly or develop drug resistance. Their new study, however, could lead to better identification of which patients with prostate cancer may respond to PARP inhibitors.
The researchers analyzed the levels of tumor DNA that circulated in the blood of 49 men with advanced prostate cancer, of whom 16 responded to treatment with a PARP inhibitor called olaparib. Among the men who responded to the drug, the team identified a median decrease of 49.6% in the DNA of the circulating cancer after 8 weeks of treatment. However, men who did not respond to olaparib showed a mean increase in circulating cancer DNA of 2.1% after 8 weeks of treatment. This finding indicates that circulating DNA levels of cancer could help clinicians identify which patients are most likely to respond to PARP inhibitors. If response rates seem low, patients could switch to alternative treatment within a few weeks.
The researchers found that they could also identify patient survival as a result of treatment with olaparib. Compared to men whose circulating DNA remained high after 8 weeks of treatment with olaparib, those with reduced circulating DNA lived an average of 7 months longer. Finally, the researchers identified markers that could help predict the patient’s likelihood of developing resistance to the olaparib. Among the patients who stopped responding to the drug, the researchers found that their cancer cells had acquired genetic changes that neutralized DNA repair mutations that made them vulnerable to the olaparib first.
While the new blood test requires further testing in a larger group of patients, the researchers believe it could pave the way for a new era of precision medicine for prostate cancer. Professor de Bono makes a final comment on the data obtained: “From these results, we were able to develop a powerful diagnostic test to be used in the near future to help doctors choose treatment, check if it works and monitor long-term cancer. We think it could be used to make clinical decisions about whether a PARP inhibitor works within a minimum of 4-8 weeks of starting therapy”.
- edited by Dr Gianfrancesco Cormaci, PhD, specialist in Clincal Biochemistry.
Goodall J et al. TOPARP-A investigators. Cancer Discov. 2017; 7(9):1006-1017.
Zhu J et al. Clin Genitourin Cancer. 2017 Dec; 15(6):e1137-e1141.
Bourton EC et al. J Cancer. 2017 Oct 23; 8(19):4048-4056.
Quigley D et al. Cancer Discov. 2017 Sep; 7(9):999-1005.