Hope for 1 in 8 men who will be diagnosed with prostate cancer

The Royal Swedish Academy of Sciences has awarded this year’s Sjoberg Prize in cancer research, worth $1 million, to Dr Arul M Chinnaiyan, for his discovery of the fusion gene responsible for more than half of all prostate cancer cases. The Director of the Michigan Centre for Translational Pathology and SP Hicks Endowed Professor of Pathology and Urology at the University of Michigan tells TOI about advances that can help improve the survival and care of affected men: What is the scale of the prostate cancer problem today? About 1 in 8 men will be diagnosed with prostate cancer in their lifetime. With the exception of skin cancer, it is the most common cancer in men. Prostate cancer is a disease of older men and rare in men under 40. What are the challenges of detecting this cancer? Can investigation via body fluids replace biopsies? Early detection of prostate cancer is challenging as the most often used blood test for prostate cancer, PSA, is a non-specific test. Also, it is often difficult to distinguish indolent (slow growing) prostate cancers from the aggressive (or high grade) version of the disease. There are several blood- or urine-based tests available to detect prostate cancer. medium89729228 How does your research contribute to improving the detection of the disease? The recurrent gene fusions we discovered are found in over 60% of prostate cancers.The most common recurrent gene fusion we identified, TMPRSS2::ERG, is found in 50% of prostate cancers. Unlike PSA which can be elevated in benign conditions such as benign prostatic hyperplasia or inflammation of the prostate, TMPRSS2::ERG is exquisitely specific for prostate cancer. It can be detected in the urine of prostate cancer patients and is incorporated in several urine-based tests for prostate cancer. Its detection can also be used clinically in challenging prostate biopsies. In terms of treatment, the gene fusions in prostate cancer are under the control of male hormones, and blocking male hormones is already an established treatment for prostate cancer. Investigations are also underway to target the gene fusion product directly or indirectly using a variety of approaches. What is the potential of your gene fusion research for other cancers? Before the discovery of recurrent gene fusions in prostate cancer, it was thought that gene fusions and translocations were major drivers of liquid cancers and rare soft tissue tumors. But we found these gene fusions in high prevalence in a common solid tumor, that being prostate cancer. After our discovery, a number of recurrent gene fusions were identified in subsets of other common solid tumors including lung cancer, breast cancer, and melanoma. Perhaps the most famous being the EML4-ALK gene fusion in lung cancer which can be directly targeted with drugs. Do the side-effects of prostate cancer’s diagnosis and treatment continue to be daunting? Yes, side-effects are associated with diagnostic prostate needle biopsies including bleeding at the biopsy site, blood in semen or urine, and infection. Most prostate needle biopsies are unnecessary. Different treatments for prostate cancer (eg radiation, surgery or hormones) are associated with a different set of side-effects which continue to be daunting. What are the ongoing processes for making detection and treatment affordable? Blood- and urine-detection tests for prostate cancer are available. They can prevent over-diagnosis and over-treatment. Next-generation anti-androgen therapies have made a major impact in the treatment of advanced prostate cancer, and some of these agents are becoming available as generics, which should make them more affordable. How do you plan to spend the Sjoberg Prize money? As this award recognises our discovery of recurrent gene fusions in prostate cancer, I plan to use this support to fund our efforts to directly and indirectly therapeutically target these and other cancer-causing transcription factors.As transcription factors have been challenging to develop drugs against, we plan to approach this from a variety of angles. What cancer research do you find notable in India? I would say in the last 5-10 years India has made significant investments in biomedical research which has allowed academic labs in India to really flourish and compete on the international stage. The biotechnology and drug development scene in India has also blossomed with these significant investments. In fact, my lab has effectively collaborated with Aurigene Biosciences out of Bangalore and recently published a paper in Nature. This work demonstrated that one can indirectly target cancer-causing transcription factors (like the prostate cancer gene fusion we discovered) by blocking their access to DNA enhancer elements. This class of compounds are in clinical development by Aurigene and they have received a good deal of press related to this drug class. In terms of prostate cancer research specifically in India, my former trainee Dr Bushra Ateeq is a professor in IIT Kanpur and has been examining the prostate cancer gene fusion and other cancer drivers with a particular focus on the Indian population. She received the Shanti Swarup Bhatnagar Prize for Science and Technology in Medical Sciences in 2020. What implications does Covid-19 vaccine research have for cancer? I would say that the tremendous success of mRNA-based vaccines against Covid-19 (eg those developed by Moderna and Pfizer) suggests that the mRNA platform may also be useful in developing vaccines for different cancers. Studies are underway by Moderna and other companies to test this in patients.Photo credit: Michigan Medicine