转移性去势抗药性前列腺癌（mCRPC）男性经常对雄激素受体信号抑制剂（ARSI）治疗产生抗药性，因此需要新的治疗方法。滋养层绒毛细胞表面抗原（Trop-2）是在前列腺癌中被识别出的跨膜蛋白，在多种恶性肿瘤中过表达。Trop-2是抗体药物联合物（ADCs）的治疗靶点。利用来自四个先前策划的mCRPC队列（n = 634）和PROMOTE研究（dbGaP accession phs001141.v1.p1，n = 88）的数据分析前列腺活检的Trop-2基因（TACSTD2）表达和治疗耐药标记。通过从外周血中捕获EpCAM或Trop-2阳性的循环肿瘤细胞来比较蛋白质（n = 15）和治疗耐药基因表达标志（n = 40）。我们在从前列腺癌细胞系生成的小鼠异种移植模型中评估了Trop-2靶向药物的疗效。我们证明了TACSTD2在来自双层和基底肿瘤的mCRPC中表达，但在神经内分泌前列腺癌患者中的表达水平较低。之前接受ARSI治疗的患者在TACSTD2表达方面没有显着差异，而具有可检测的AR-V7表达的患者表达增加。我们观察到Trop-2可作为分离循环肿瘤细胞的细胞表面靶点，这可能作为ADCs的预测性生物标志物。我们还证明了前列腺癌细胞系异种移植瘤可以在体内通过标记的抗Trop-2药物特异性靶向。这些结果支持进一步研究Trop-2作为mCRPC治疗和诊断靶点的可行性。

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).Trop-2 gene (TACSTD2) 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.We demonstrated TACSTD2 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 TACSTD2 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 in vivo.These results support further studies on Trop-2 as a therapeutic and diagnostic target for mCRPC.