Project Grant R01CA296366

This National Cancer Institute (NCI) Cancer Biology Research (CFDA 93.396) Project Grant awards $498,775 to Stony Brook University, with performance through June 30, 2031, to investigate targetable mechanisms driving altered cell states in castration-resistant prostate cancer (CRPC). The research dissects the emergence and expansion of a rare cellular subpopulation expressing follistatin (FST) that develops resistance to androgen-deprivation therapy (ADT). The project deliverables will include fundamental scientific findings on how FST overexpression functions as a novel mechanism of castration resistance, identification of specific markers and pathways sustaining resistant cell subtypes, and peer-reviewed publications advancing understanding of phenotypic cellular diversification in prostate cancer progression. Preliminary single-cell transcriptomic studies indicate that FST-expressing cells exist in low frequency within treatment-naive tumors and expand significantly during the transition to CRPC, suggesting that characterizing these pre-existing resistant populations may inform therapeutic strategies to prevent emergence of treatment-refractory disease.

The research addresses a critical gap in cancer cell biology by investigating whether drug-resistant cellular states pre-exist within tumors and expand under therapeutic selection pressure, or emerge de novo during disease progression. Gaining mechanistic insight into the properties and survival pathways sustaining FST-overexpressing cell populations is intended to advance current therapeutic approaches toward potentially curative treatments for advanced prostate cancer, consistent with the NCI's fundamental mission to provide knowledge on cancer etiology and mechanism that informs prevention, detection, and treatment strategies.