Data from Expression and therapeutic targeting of Trop-2 in treatment resistant prostate cancer

Abstract

<div>Abstract<p>PURPOSE. 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 (ADCs). Experimental Design. 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 (n = 634) and the PROMOTE study (dbGaP accession phs001141.v1.p1, n = 88). EpCAM or Trop-2 positive circulating tumor cells were captured from peripheral blood for comparison of protein (n=15) and gene expression signatures of treatment resistance (n=40). We assessed the efficacy of Trop-2 targeting agents in a mouse xenograft model generated from prostate cancer cell lines. RESULTS. We demonstrated <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 AR-V7 expression showed increased expression. We observed that Trop-2 can serve as a cell surface target for isolating circulating tumor cells, 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 </i><i>vivo</i>. CONCLUSION. These results support further studies on Trop-2 as a therapeutic and diagnostic target for mCRPC.</p></div>