Scientists at The Institute of Cancer Research, London, have identified a genetic aberration in prostate cancer cells that could make them susceptible to treatment with the targeted drug olaparib. This discovery is based on the finding that cancer cells which have 'lost' the DNA repair protein RNASEH2B are killed when treated with PARP inhibitors, a class of drugs that includes olaparib.
The RNASEH2B gene is crucial for repairing certain types of DNA damage. When this gene is deleted or 'lost' during cell division, it no longer functions properly, making the cancer cells vulnerable to PARP inhibitors. This research, published in the Journal of Clinical Investigation, suggests that olaparib, which has already transformed the treatment of prostate cancers caused by BRCA1, BRCA2, and ATM mutations, could be effective for a wider group of men with advanced prostate cancer.
In a study involving biopsies from 124 patients with advanced prostate cancer, researchers found that RNASEH2B loss was common, with 44% of patients showing loss in at least 50% of their cancer cells. Furthermore, 20% of patients had RNASEH2B loss in 75% of their cancer cells. The study also evaluated biopsy samples from patients without BRCA1 and BRCA2 mutations who participated in the TOPARP-A and TOPARP-B clinical trials. It was observed that the number of cells with RNASEH2B loss decreased in 13 out of 18 patients following PARP inhibitor treatment, with six patients also experiencing a decline in circulating tumour cells (CTCs).
This research builds on earlier findings that olaparib could be successful in treating more men with prostate cancer and identifies the RNASEH2B gene as a potential target for treatment. The findings are expected to lead to further trials of olaparib in prostate cancer, aiming to explore its effectiveness in a larger patient population by identifying individuals with RNASEH2B aberrations.
Professor Johann de Bono of The Institute of Cancer Research, London, emphasized the significance of this discovery, stating that it represents a substantial advance in expanding the number of patients who could benefit from PARP inhibitors, improving overall survival and quality of life for more men with advanced prostate cancer. Further research is urgently needed to validate these findings and develop tests to identify tumours sensitive to PARP inhibitors beyond BRCA gene mutations, offering a new treatment option for patients with advanced prostate cancer.
