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2021 Michael and Patricia Berns-PCF Young Investigator Award

Using 5-Hydroxymethylcytosine (5hmC) Sequencing to Investigate Treatment Resistance and Develop Liquid Biomarkers for Advanced Prostate Cancer

Martin Sjöström, MD, PhD
University of California, San Francisco

Mentors: Felix. Feng, MD, David Quigley, PhD, Alexander Wyatt, DPhil

Description:

  • Castration resistant prostate cancer (CRPC) is an advanced from of prostate cancer that has developed resistance to androgen receptor (AR)-targeting therapies. One mechanism of AR-therapy resistance is lineage plasticity, a phenomenon in which prostate cells lose prostate cell features and gain features of other cell types such as neuroendocrine cells.
  • Lineage plasticity is driven in part by epigenetic changes, where chemical modifications that control which genes a cell can and cannot express are altered.
  • Dr. Martin Sjöström is studying epigenetic modifications that drive lineage plasticity and treatment resistance in prostate cancer.
  • In this project, a comprehensive map of genome-wide epigenetic patterns of lineage plasticity in metastatic CRPC will be developed.
  • Epigenetics-based liquid biomarkers using cell-free DNA (cfDNA) will be developed that can predict pre-existing and acquired treatment responses or resistance to AR-targeted therapy or taxane chemotherapy.
  • If successful, this project will create a comprehensive map of epigenetic modifications that drive CRPC lineage plasticity and treatment resistance and develop liquid biopsy-based epigenetic biomarkers to predict treatment response and resistance.

What this means to patients: Lineage plasticity is a major mechanism underlying the development of aggressive, treatment resistant prostate cancer, and is largely driven by epigenetic alterations. Dr. Sjöström will comprehensively map epigenetic alterations that promote lineage plasticity and use this information to develop blood-based biomarkers to predict treatment outcomes in patients. This may inform new treatment strategies to overcome resistance and increase the availability of precision medicine approaches for patients.