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Expression and Therapeutic Targeting of TROP-2 in Treatment-Resistant Prostate Cancer

Jamie M Sperger1,2, Kyle T Helzer3, Charlotte N Stahlfeld2

  • 1Department of Medicine, University of Wisconsin-Madison, Madison, Wisconsin.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|March 20, 2023
PubMed
Abstract

Insights

Trophoblastic cell-surface antigen (TROP-2) is a viable target for new metastatic castration-resistant prostate cancer (mCRPC) therapies. TROP-2 expression in mCRPC suggests its potential as a predictive biomarker for antibody-drug conjugates (ADCs).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) frequently develops resistance to androgen receptor signaling inhibitors (ARSIs).
  • Novel therapeutic strategies are crucial for managing treatment-resistant mCRPC.
  • Trophoblastic cell-surface antigen (TROP-2) is overexpressed in various cancers, including prostate cancer, making it a potential therapeutic target.

Purpose of the Study:

  • To investigate Trophoblastic cell-surface antigen (TROP-2) gene (TACSTD2) expression in mCRPC.
  • To evaluate TROP-2 as a potential biomarker for treatment resistance and as a target for antibody-drug conjugates (ADCs).
  • To assess the efficacy of TROP-2-targeting agents in preclinical models.

Main Methods:

  • Analysis of TACSTD2 expression in four mCRPC cohorts (n=634) and the PROMOTE study (n=88).
  • Isolation and analysis of TROP-2-positive circulating tumor cells (CTCs) from peripheral blood.
  • Assessment of TROP-2-targeting agents in a mouse xenograft model of prostate cancer.

Main Results:

  • TACSTD2 expression was detected in luminal and basal mCRPC tumors, with lower levels in neuroendocrine prostate cancer.
  • No significant difference in TACSTD2 expression was observed in patients previously treated with ARSI.
  • Increased TACSTD2 expression correlated with detectable AR-V7 expression.
  • TROP-2 served as a cell surface target for CTC isolation, indicating potential as a predictive biomarker for ADCs.
  • In vivo studies demonstrated specific targeting of prostate cancer xenografts by labeled anti-TROP-2 agents.

Conclusions:

  • TROP-2 is expressed in mCRPC and can be targeted therapeutically.
  • TROP-2 holds promise as a predictive biomarker for ADC efficacy in mCRPC.
  • Further research into TROP-2 as a therapeutic and diagnostic target for mCRPC is warranted.

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