A study led by scientists from the Center for Genetic Epidemiology at the Keck School of Medicine of USC and USC Norris Comprehensive Cancer Center has made a significant leap in our understanding of aggressive prostate cancer.

In this unprecedented research effort, mutations in eleven genes associated with aggressive forms of prostate cancer have been pinpointed. This momentous discovery has the potential to reshape how we approach the diagnosis, treatment, and prevention of this deadly disease.

Prostate cancer is a complex and heterogeneous disease, and the quest to tailor treatment to individual patients has never been more crucial. Genetic tests have been a beacon of hope in this endeavour, helping oncologists customise care for individuals with aggressive prostate cancer. These tests offer valuable insights that can inform treatment decisions, and some targeted therapies have already proven effective against inherited prostate cancers. Moreover, these test results can initiate genetic screening among family members, providing them with the opportunity to take proactive measures to reduce their risk and collaborate with healthcare professionals for early detection.

The study, published in JAMA Oncology, represents a monumental leap forward in our comprehension of the genetic underpinnings of aggressive prostate cancer. It explores the exome, the fundamental sections of the genetic code responsible for encoding proteins. With an astounding dataset of approximately 17,500 prostate cancer patients, this study is the largest-scale investigation into prostate cancer genetics to date.

Christopher Haiman, the corresponding author of the study and a prominent figure in the field of cancer research, emphasised the significance of large-scale studies in shaping the landscape of genetic testing. He stated that very large studies are needed to inform the creation of gene panels used for testing. Some of the genes currently included in these panels were based on small-scale studies and did not exhibit any association with prostate cancer in this extensive research. Conversely, the study also suggested that some genes not currently part of these panels might warrant inclusion. While the results are not entirely definitive, they underscore the need for further exploration to determine which genes should take precedence in testing.

This research effort amalgamated data from eighteen studies conducted across the United States, Europe, and Australia. The team meticulously analysed blood samples from prostate cancer patients of European descent, splitting them into two groups: those with aggressive disease (9,185 patients) and those without (8,361 patients). This dichotomy allowed them to compare the frequency of mutations between the two groups, shedding light on the genetic factors underlying aggressive prostate cancer.

The research unfolded in two distinct phases. First, Haiman and his colleagues sequenced the entire set of protein-coding genes in almost a third of the participants. In the second phase, they homed in on a subset of 1,749 genes that had either been previously associated with cancer or emerged as promising candidates in the initial sequencing. This subset included nearly 200 genes involved in DNA repair, a process vital for maintaining genetic integrity. Disruptions in this process can create opportunities for cancerous cells to thrive.

Among the myriad genes investigated, eleven genes stood out as having mutations significantly linked to aggressive prostate cancer. Notably, one of these genes is BRCA2, which is also notorious for its connection to breast cancer. This discovery, coupled with the revelation that some genes currently featured in genetic test panels are not associated with the risk of aggressive disease, could revolutionize the landscape of prostate cancer treatment and screening.

Haiman emphasised that mutations identified in this study were also detected in some patients without aggressive disease. This implies that these mutations may increase the risk of their cancer advancing in the future. While current screening efforts primarily target men with advanced disease or a family history of prostate cancer, identifying patients with less advanced disease who carry these genetic variants could facilitate early intervention with targeted treatments.

However, this study comes with two important caveats. Firstly, despite its considerable size, certain mutations driving the risk of aggressive prostate cancer are exceptionally rare, necessitating even larger studies for more comprehensive insights. Secondly, the findings of this research may not be generalizable beyond the population of European descent. Christopher Haiman emphasised the need for similar efforts to take place in populations of African ancestry, underlining the importance of inclusivity and diversity in genetic research.

In conclusion, the international research team led by scientists at the Keck School of Medicine of USC and USC Norris Comprehensive Cancer Center has explored the genetic landscape of aggressive prostate cancer. Their study, encompassing thousands of patients and revealing crucial mutations in genes, holds immense promise for advancing the field of prostate cancer diagnosis, treatment, and prevention. As science continues to evolve, this research will serve as a beacon of hope for patients and families affected by this devastating disease, paving the way for more precise and effective strategies in the fight against prostate cancer.