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2022 PCF Challenge Award

Targeting B7-H3 in Aggressive Variant Prostate Cancer

Principal Investigators: Di Zhao, PhD (The University of Texas MD Anderson Cancer Center), Ana Aparicio, MD (The University of Texas MD Anderson Cancer Center), Sangeeta Goswami, MD, PhD (The University of Texas MD Anderson Cancer Center)

Co-Investigator: Wenyi Wang, PhD (The University of Texas MD Anderson Cancer Center)

Young Investigator: Wei Shi, PhD (The University of Texas MD Anderson Cancer Center)

Collaborators: Nora Navone, MD, PhD (The University of Texas MD Anderson Cancer Center), James Allison, PhD (The University of Texas MD Anderson Cancer Center)

Description:

  • Aggressive variant prostate cancer (AVPC) is a rapidly lethal form of metastatic castration resistant prostate cancer (mCRPC) that can be identified by clinical and molecular features. AVPCs have dismal prognoses and effective therapies for this subset are urgently needed.
  • Di Zhao and team have previously demonstrated that AVPCs commonly express high levels of B7-H3, an immune-regulatory protein that has emerged as a promising target for cancer immunotherapy. They also found that depletion of B7-H3 in AVPC models impaired tumor progression and reversed the immunosuppressive tumor microenvironment.
  • These data suggest that B7-H3 may be a promising therapeutic target for patients with AVPC.
  • In this project, Dr. Zhao and team will use cutting edge digital pathology to assess the expression patterns and role of B7-H3 in mCRPC and AVPC. The association between B7-H3 patterns with treatment responses and clinical outcomes will be investigated.
  • The mechanisms that cause B7-H3 overexpression in AVPC will be determined.
  • DS-7300 is a B7-H3-targeted antibody drug conjugate that is currently under pharmaceutical development for various types of cancer, that has shown promising activity in early clinical trials. The team will investigate the efficacy and mechanisms of action of DS-7300 treatment in preclinical AVPC models.
  • If successful, this project will provide biological rationale for clinical trials testing B7-H3-targeting treatments in patients with AVPC.

What this means to patients:  AVPC is a highly aggressive and lethal form of advanced prostate cancer for which there are currently no effective treatments.  Dr. Zhao and team will determine the role of B7-H3 in AVPC and mCRPC and its potential as a therapeutic target, thus laying the foundation for clinical trials testing B7-H3-targeting treatments in patients with currently untreatable forms of aggressive prostate cancer.