Ben Ho Park, MD, PhD

Improving the clinical utility of liquid biopsies to detect circulating tumor DNA and inform breast cancer management.

Impact

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.

Progress Thus Far

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.

What’s next

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.