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The Patrick C. Walsh Prostate Cancer Research Fund
Developing a “Liquid Biopsy” of Metastatic Prostate Cancer
Although there have never been better therapies for metastatic prostate cancer, says Ben Ho Park, M.D., Ph.D., the Irene and Bernard L. Schwartz Scholar, eventually drug resistance still develops and the cancer continues to gr ow. Thus, scientists must find the genetic causes that drive these processes, says Park, an Oncologist with a joint appointment in the Department of Chemical and Biomedical Engineering. “Recently, there has been renewed interest in androgen receptor (AR) mutations that are found in metastatic sites after hormonal therapy,” he notes. “The problem with these studies is that often, just one biopsy at a single site has been used to document whether AR mutations are there or not. But because there are many different types of cancer cells involved, a single-site biopsy is likely not enough to giv e us the correct picture.”
All cells, including cancer cells, shed DNA into the bloodstream. “Only recently has technology matured to the point where we can accurately identify these cancer DNA molecules in the blood,” Park says. He believes looking at this “circulating plasma tumor DNA,” called ptDNA, may give better insight into the true nature of the cancer cells that need to be tr eated. Using a technology called droplet digital polymerase chain reaction, or ddPCR, “we are able to detect cancer mutations in the blood with exquisite sensitivity and specificity — giving us a liquid biopsy, which promises to overcome the constraints of tissue biopsies.”
However, the technology for ptDNA analysis is not yet ready for routine clinical practice, Park says. “Most significantly, the variable and exhaustible amount of plasma DNA that can be obtained per patient sample can be a limiting factor.” In a study with scientist Paula Hurley, Ph.D., the Beth W. and A. Ross Myers Scholar, Park is hoping to find a way to “immortalize” plasma DNA by “merging existing technologies in a unique way, which will allow us to endlessly amplify plasma DNA with perfect fidelity.” If this proves successful, this plan will “significantly improve and impact the ability to move ptDNA forward as useful biomarkers” that will give scientists the specific rundown of the cells in a tumor — and sugges t how best to kill them.