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

Abstract

<div>AbstractPurpose:<p>Men with metastatic castration-resistant prostate cancer (mCRPC) frequently develop resistance to androgen receptor signaling inhibitor (ARSI) treatment; therefore, new therapies are needed. Trophoblastic cell-surface antigen (TROP-2) is a transmembrane protein identified in prostate cancer and overexpressed in multiple malignancies. TROP-2 is a therapeutic target for antibody–drug conjugates (ADC).</p>Experimental Design:<p>TROP-2 gene (<i>TACSTD2</i>) expression and markers of treatment resistance from prostate biopsies were analyzed using data from four previously curated cohorts of mCRPC (<i>n</i> = 634) and the PROMOTE study (dbGaP accession phs001141.v1.p1, <i>n</i> = 88). EPCAM or TROP-2–positive circulating tumor cells (CTC) were captured from peripheral blood for comparison of protein (<i>n</i> = 15) and gene expression signatures of treatment resistance (<i>n</i> = 40). We assessed the efficacy of TROP-2–targeting agents in a mouse xenograft model generated from prostate cancer cell lines.</p>Results:<p>We demonstrated that <i>TACSTD2</i> is expressed in mCRPC from luminal and basal tumors but at lower levels in patients with neuroendocrine prostate cancer. Patients previously treated with ARSI showed no significant difference in <i>TACSTD2</i> expression, whereas patients with detectable <i>AR-V7</i> expression showed increased expression. We observed that TROP-2 can serve as a cell surface target for isolating CTCs, which may serve as a predictive biomarker for ADCs. We also demonstrated that prostate cancer cell line xenografts can be targeted specifically by labeled anti–TROP-2 agents <i>in vivo</i>.</p>Conclusions:<p>These results support further studies on TROP-2 as a therapeutic and diagnostic target for mCRPC.</p></div>