Dr. Vasan Yegnasubramanian
Currently, Dr. Yegnasubramanian is working with colleagues in laboratory medicine to develop a clinical sequencing laboratory focused on translating genetic and epigenetic research and findings into clinical tests that will guide cancer diagnosis, risk classifications, and therapy. The Kimmel Cancer Center’s strength in translational medicine has uniquely positioned our Center to bridge the research laboratory and the clinic so that these advances can make their way more quickly to patients. “There are few places that have the human assets of the Kimmel Cancer Center,” says Dr. Yegnasubramanian, assistant professor of oncology and environmental health sciences. “In the same building, we have clinical experts, laboratory medicine experts, and genomics experts all thinking about this, working with each other and figuring out how to move this science and technology forward. This strength is putting us ahead.”
In the clinical sequencing facility, he and his team will focus first on acute myeloid leukemia (AML), a type of cancer of blood cells where there is already a great deal of information on cellular and genetic alterations used to make treatment decisions. Initially, research and clinical teams will use the new technology to update tests. In a single, cutting-edge test, they will now be able to screen for a variety of treatment-impacting alterations instead of performing a separate test for each alteration. In the future, they will broaden the work to include other diseases and incorporate new genetic discoveries.
Dr. Yegnasubramanian’s role in guiding both the research and clinical sequencing laboratories will allow seamless translation of new research findings in cancer genetics and epigenetics to the clinical laboratory. This will be accomplished, for instance, by deploying similar technology platforms in the research and clinical labs. As a result, if there is a question that investigators can ask where genomics can help monitor a cancer or determine which patients should get a particular treatment, the two laboratories will operate in conjunction, with the capability to share information, eliminating the lag time between discovery and clinical implementation.
Using Cancer DNA to Improve Prostate Cancer Treatment
Some of the greatest potential of personalized medicine is in using our new knowledge about the biology of cancer to get the right treatments to the right patients. With this comes the ability to target therapies, but just as important, to accurately and scientifically identify patients who could be spared invasive treatments and their associated risks and complications. Current research at Johns Hopkins reveals significant overtreatment of prostate cancer. The science finds that many older men with slow-growing, non-aggressive forms of prostate cancer could safely forgo treatment, yet most of them (as many as 90 percent) choose to have treatment and, as a result, may needlessly suffer from complications, including impotence, incontinence and other quality-of-life-changing events. Dr. Yegnasubramanian believes a simple but accurate test that would provide clear biological data to distinguish aggressive prostate cancers from the slow growing type, which could be left alone, would change this and significantly improve outcomes for men.
As director of a prostate cancer genetics and epigenetics laboratory, Dr. Yegnasubramanian is working towards creating such a test. He is looking to epigenetic alterations (potentially reversible changes in the interpretation of the genetic code) in prostate cancer. Currently, the only way to correctly distinguish an aggressive prostate cancer from a harmless one is to examine the tumor after the prostate is removed in a surgical procedure known as prostatectomy. Dr. Yegnasubramanian and team are working to develop a test that could make the determination prior to surgery and potentially spare many men from prostatectomy. His team is currently using a technology developed in their laboratory to study human tumor samples from both the lethal and indolent forms of prostate cancer. His goal is to identify a panel of epigenetic biomarkers that are detectable in blood and urine and could be used to separate aggressive prostate cancers that would be suited to surgical and radiation treatments from ones that would best be managed with less invasive forms of treatment, and potentially no treatment at all.
Dr. Yegnasubramanian also is collaborating with one of the world’s leading cancer genetics expert, Kenneth Kinzler, Ph.D., and a foremost epigenetics expert, Stephen Baylin, M.D., as well as clinical prostate cancer investigators Michael Carducci, M.D., Ph.D., and Mario Eisenberger, M.D., to better understand how differences in the prostate cancer genome and epigenome impact treatment outcomes. In prostate cancer that recurs and spreads after treatment, the first line approach is hormone (androgen) suppression therapy—in essence cutting off the supply of hormones that are believed to be fueling the cancer. At this stage, most men will survive about four years. However, our investigators have found that there are extremes in patient survival that could provide important new clues about the disease. A subset of men progress rapidly and may die within the first year of their recurrence, but another subset appear to be cured by the hormone suppression therapy, living for years without any sign of cancer recurrence. Dr. Yegnasubramanian and team believe the reasons for these differences are hidden within the genome and epigenome of prostate cancer, and they are hoping to use the power of next generation sequencing to uncover the biological differences. What is different about the cancer DNA of long-term survivors versus those men who have a very rapid progression? Their findings would give clinicians the opportunity to direct more intensive therapies to men whose cancer DNA predestines them to be less responsive to standard treatments and give less therapy, or stop treatment altogether, in men whose cancer DNA points to long-term remission. What they learn about the extremes of treatment responses should also help all men with prostate cancer by shedding new light on other mechanisms that could be targeted in treatment. In addition, what Dr. Yegnasubramanian and team uncover about the genetic and epigenetic basis of extremes of therapeutic response could likely be applied to other cancers.