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2022 Sage & Tony Minella – PCF Young Investigator Award

PTEN/P53 Altered Prostate Cancer has Unique Role for Tumor Associated Macrophages upon Apalutamide Resistance

Woogwang Sim, PhD
University of California, San Francisco (UCSF)

Description:

  • A major problem in prostate cancer is the development of resistance to hormonal therapies and progression to castration resistant prostate cancer (CRPC), which can be driven by several types of molecular alterations.
  • Dr. Woogwang Sim is studying the biology of an aggressive form of CRPC driven by combined alterations in PTEN and P53, which occur in ~15% of mCRPC cases.
  • Dr. Sim has previously found that PTEN/P53-mutant CRPC have a substantial increase in tumor-associated macrophages, a phenomenon which is not seen in a form of CRPC driven instead by RB1 and P53 mutations.
  • In this project, Dr. Sim will determine whether tumor associated macrophages contribute to androgen receptor (AR)-targeted therapy resistance in PTEN/TP53-mutant prostate cancer.
  • The molecular interactions between tumor associated macrophages and tumor cells in AR therapy-resistant PTEN/TP53-mutant prostate cancer will be investigated.
  • If successful, this project will define the role of tumor associated macrophages in PTEN/TP53-mutant prostate cancers and AR therapy resistance, and may identify new ways to target interactions between tumor associated macrophages and tumor cells.

What this means to patients: PTEN/P53-mutant CRPC is a highly aggressive form of CRPC that comprises ~15% of CRPC cases. Dr. Sim and team will determine whether tumor associated macrophages are critical drivers of treatment resistance and progression in PTEN/P53 mutant CRPC, which would provide rationale for targeting tumor associated macrophages as a strategy to prevent or delay resistance to AR-targeted therapies.