Vanderbilt University Medical Center Nashville, Tennessee
Director, Vanderbilt-Ingram Cancer Center Director, Division of Hematology and Oncology Professor of Medicine Associate Director for Translational Research Director for Precision Oncology
Member, BCRF Scientific Advisory Board
Improving the clinical utility of liquid biopsies to detect circulating tumor DNA and inform breast cancer management.
Liquid biopsy is a non-invasive technique currently used in the clinic for diagnosis and prognosis in breast and other cancers. Liquid biopsies are used to isolate cell-free DNA molecules shed from normal and cancerous cells into the blood. While tumor cells shed their DNA into the bloodstream, known as circulating tumor DNA (ctDNA), the relatively small quantity in a patient’s blood is a major impediment to maximizing the utility of liquid biopsies. Significant improvements in this technology have pushed the limits of detection such that even one ctDNA molecule in a million normal cell-free DNA molecules can be isolated from blood. However, obtaining a million cell-free DNA molecules from a single blood draw is often not feasible and so the clinical sensitivity of liquid biopsies is limited. Dr. Park and his team have shown that key genes that mediate cell death pathways also influence cell-free DNA release from cells. They are leveraging their findings to develop drugs that could increase the amount of ctDNA from cancer cells and vastly improve the accuracy of liquid biopsies and expand their use in the clinic to inform breast cancer care.
Dr. Park and his colleagues have been characterizing the genes and pathways previously identified in a genetic screen and also assessing their ability to increase cell-free DNA release. In addition, the team has obtained patient samples from ongoing clinical trials to determine if currently available drugs are able to increase cell-free DNA and ctDNA release.
Before these results can be tested in the clinic, Dr. Park and his team will validate these findings in laboratory models. This will be accomplished by comparing the amount of ctDNA shed from cancer cells with and without the currently available drugs thought to promote release of ctDNA. Ongoing studies will also allow Dr. Park’s team to assess the effectiveness of these drugs and determine the optimal dose needed to increase ctDNA shedding. If this strategy for augmenting ctDNA release proves successful, this would be a major step towards applying liquid biopsy for ctDNA detection as a tool for the clinical management of patients with breast cancer.
Ben Ho Park, MD, PhD, an internationally renowned breast cancer expert, was recently appointed as the co-leader of the Breast Cancer Research Program, Associate Director for Translational Research and Director of Precision Oncology at Vanderbilt-Ingram Cancer Center. Dr. Park is from Saginaw, MI and received his bachelor’s degree from The University of Chicago and then completed a dual MD-PhD training program at The University of Pennsylvania School of Medicine. After completing a residency in Internal Medicine and Hematology/Oncology Fellowship Training at The Hospital of The University of Pennsylvania, he finished a postdoctoral research fellowship in cancer genetics in the laboratory of Dr. Bert Vogelstein at Johns Hopkins University, and then joined the faculty in 2002 in the Breast Cancer Program. At Hopkins he was Professor of Oncology, Associate Director for Education and Research Training, as well as Associate Dean for Postdoctoral Affairs prior to joining the faculty at Vanderbilt University Medical Center.
2008
The Delta Air Lines Award
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