2023 Todd Boehly – PCF Young Investigator Award

Discovering Combination Therapeutic Targets in Castration-Resistant Prostate Cancer using Highly Multiplexed CRISPR Chromatin Perturbations

Chris Hsiung, MD, PhD
Stanford University

Mentors: Luke Gilbert, Felix Feng, Howard Chang

Description:

• Castration-resistant prostate cancers (CRPC) can exhibit significant phenotypic plasticity. In one extreme form of this plasticity, CRPC can acquire treatment resistance by adopting the lineage identity of another cell type, neuroendocrine cells. This plasticity creates highly aggressive prostate cancer subtypes for which new treatment approaches are urgently needed. Whether these aggressive CRPC phenotypes can be reprogrammed to more benign states or eliminated without toxicity to other tissues remains uncertain.
• Dr. Chris Hsiung is developing and applying novel combinatorial functional genomics approaches to efficiently screen millions of combinations of targets in the genome of CRPC cell models to identify combinations that when targeted can prevent or reverse the transition to aggressive forms of CRPC.
• Using a conceptually related approach for nominating combination therapeutic targets, Dr. Chris Hsiung is developing next-generation CRISPR therapeutic strategies with the goal of targeting key oncogenes driving aggressive CRPC while minimizing off-tissue toxicity.

What this means to patients: New treatments are needed for patients with aggressive forms of CRPC, including neuroendocrine prostate cancer. Dr. Hsiung and team will develop and apply a novel CRISPR gene targeting approach that enables efficiently testing millions of combinations of potential therapeutic targets discover specific combinations that can prevent or reverse the development of aggressive forms of CRPC. This efficient large-scale discovery approach can lead to the development of next-generation combination therapeutics for treating aggressive forms of CRPC.