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2022 Silas Chou – PCF Young Investigator Award

Targeting SWI/SNF Chromatin Remodeling Complex to Combat Castrate-Resistant Prostate Cancer

Lanbo Xiao, PhD
University of Michigan

Description:

  • Although androgen deprivation therapy (ADT) is the most efficient clinical regimen for advanced prostate cancer, nearly all ADT-treated individuals will eventually develop resistance and progress to the castration resistant prostate cancer (CRPC) state. Novel therapeutic strategies are urgently needed.
  • SWI/SNF complex is a regulator of the 3D structure of chromatin, thereby controlling which genes can and cannot be expressed. SWI/SNF genes are mutated in ~20% of human cancers, and have been implicated in prostate cancer progression to CRPC.
  • Dr. Lanbo Xiao is studying the role of the SWI/SNF complex as a driver and therapeutic target in prostate cancer.
  • In this project, Dr. Xiao and team will test the efficacy of a novel “PROTAC” drug that degrades the ATPase subunits of SWI/SNF complex , SMARCA2 and SMARCA4, in preclinical models of CRPC.
  • The mechanisms by which SWI/SNF complex alters anti-tumor immune cells in the tumor microenvironment will be investigated. Whether targeting SWI/SNF complex reverts immune alterations will be determined.
  • The role of SWI/SNF in the development of neuroendocrine prostate cancer (NEPC), a highly aggressive form of CRPC will also be studied.
  • If successful, this project will deepen our knowledge of the function of the SWI/SNF complex in prostate cancer biology and shed light on future applications for SWI/SNF-targeting therapeutics in advanced prostate cancer.

What this means to patients: New treatments are urgently needed for patients with advanced prostate cancer. Dr. Xiao’s project will provide preclinical rationale for a new SWI/SNF-targeting treatment in CRPC, setting the stage for clinical trials. This project will also define the role of SWI/SNF in altering anti-tumor immunity and in the development of NEPC, a highly lethal form of prostate cancer.