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2024 American Cancer Society – PCF Young Investigator Award

Translational Applications of Epigenomic Liquid Biopsy to Advance Prostate Cancer Treatment.

Sylvan Baca, MD, PhD
Harvard: Dana-Farber Cancer Institute

Mentors: Michael Freedman, MD; Himisha Beltran, MD

Description:

  • “Liquid biopsies” are blood tests to evaluate molecular features of cancer. These tests are increasingly being used to guide cancer care, and help to avoid invasive and painful tumor biopsies.
  • Dr. Sylvan Baca and team have developed a novel platform for liquid biopsy called “cell-free ChIP-seq” that can measure epigenetic changes in cancer from patient plasma. This platform allows study of gene regulatory programs that drive prostate cancer, at a scale that is not feasible using clinical tumor specimens. 
  • In this project, Dr. Baca will determine whether the cell-free ChIP-seq platform can dynamically measure the activity and inhibition of the Androgen Receptor (AR) in patients with prostate cancer. 
  • Cell-free ChIP-seq will be used to characterize key oncogenic drivers and gene regulatory programs in double-negative prostate cancer (DNPC), an aggressive subclass of prostate cancer that lacks both AR expression and markers of neuroendocrine differentiation. 
  • Cell-free ChIP-seq will also be used to identify gene regulatory biomarkers of resistance to 177Lu-PSMA-617 (Pluvicto®) from plasma. 
  • If successful, this project will establish the first blood-based test of AR activity in prostate cancer, which could be used for disease monitoring, evaluating treatment response, and guiding therapy. This project would also provide key insights into the biology of DNPC and improve our understanding of how resistance develops to 177Lu-PSMA-617.

What this means to patients: The ability to study and monitor prostate cancer gene regulation using patient plasma will accelerate the development of new and improved treatments. In this project, Dr. Sylvan Baca is using a liquid biopsy platform to develop dynamic and biologically informative biomarkers of AR activity and 177Lu-PSMA-617 treatment response, and to identify key drivers of the highly aggressive DNPC prostate cancer subtype. These studies will inform drug development efforts targeting these aggressive cancers.