Trop2 is a driver of metastatic prostate cancer with neuroendocrine phenotype via PARP1

Significance NEPC is a highly aggressive subtype of prostate cancer that is increasing in incidence, likely due to use of new secondary androgen deprivation therapies. Here, we demonstrate that Trop2 is significantly elevated in CRPC and NEPC and represents a driver of metastatic NEPC. Trop2 overexpression increases tumor growth, drives metastasis and neuroendocrine phenotype, and significantly increases PARP1 levels. Inhibition of PARP1 in Trop2-driven NEPC significantly decreases neuroendocrine features, tumor growth, and metastatic colonization in vivo, suggesting that PARP1 inhibitors may represent a promising therapeutic strategy for metastatic prostate cancer expressing high levels of Trop2.