Our Prostate Cancer theme is committed to advancing the development and evaluation of new diagnostic techniques and treatment options based on the genetic make-up of tumours. Significant progress has been made in uncovering of the genetic causes of prostate cancer, which have enhanced our ability to identify those at risk of the disease. Our research has also led to major advances in the development of new treatments such as abiraterone, enzalutamide, cabazitaxel and radium-233, which will improve outcomes for patients. Predicting risk of prostate cancer Professor Ros Eeles has led a number of major international studies to identify genetic variations associated with prostate cancer risk including the PRACTICAL study, an international consortium of 109 groups discovered 106 genetic variants. A more recent study has identified a further 63 new genetic variations, bringing the total number of identified genetic risk factors to over 160. The study, which compared the DNA profiles of almost 80,000 prostate cancer patients with over 50,000 healthy male participants. These findings improve the ability to predict those at risk of developing prostate cancer and provide an insight into the genetic causes of the disease, potentially leading to new treatment options. Professor Eeles is exploring this further in a European Research Council (ERC)-funded study, BARCODE. In BARCODE, genetic profiling of 5000 men, identified through collaborations with General Practitioners (GPs), is being carried out. Results of this approach will be used to determine if a higher proportion of clinically significant disease is identified. The study will provide further evidence to support the use genetic profiling in order to triage for screening invitations in the future. With BRC support, Professor Eeles has developed, validated, and piloted a genetic test that detects both common and rare genetic variants. They have obtained follow-on funding from NIHR PGfAR (£3m) to expand the pilot from 200 to 2000 men and include unaffected men at high risk of developing cancer that could benefit from targeted prostate cancer screening. By 2030, this programme aims to generate the evidence and resources to support the adoption of the genetic test panel onto the National Genomic Test Directory and into routine practice. Gene-targeted treatments The TOPARP trial, a two-part study led by researchers at the ICR and The Royal Marsden, has uncovered that some patients with advanced prostate cancer could benefit from olaparib, a drug approved for use in breast and ovarian cancer. The trial found that a group of prostate cancer patients with mutations in genes involved in DNA repair, most notably the BRCA genes, were likely to benefit from treatment with olaparib. The drug was found to delay disease progression for over a year in 35% of patients with BRCA mutations. This led to a larger phase III trial of the drug which showed improvement in outcomes for prostate cancer patients with mutations in DNA repair genes treated with olaparib compared to standard therapy. Based on these results olaparib was approved for these patients by the FDA and EMA in 2020. Liquid biopsies to test for drug resistance The BRC has supported the development of a new test which analyses cancer DNA in the bloodstream to predict how prostate cancer patients will respond to the commonly used drug abiraterone. Abiraterone, which was discovered and developed by researchers at the ICR and The Royal Marsden, is used to treat castration-resistant prostate cancer, however resistance can develop in 30-60% of patients. The test - a ‘liquid biopsy’ - looks for the presence of a protein called AR-V7, which has been associated with resistance to abiraterone. It is now thought that the development of drugs which reduce the levels of AR-V7 could improve response to abiraterone and therefore improve outcomes for patients. A recent study discovered that mutations to the AR gene were associated with resistance to abiraterone, importantly, the test can detect mutations to the AR gene months before drug-resistance becomes apparent.