NUAK2 is a therapeutically tractable regulator of RNA splicing and tumor progression in neuroendocrine prostate cancer.

ABSTRACT: Prostate cancer (PC) remains the second leading cause of cancer-related mortality in men. The emergence of treatment-emergent neuroendocrine prostate cancer (NEPC) arising from androgen receptor (AR) pathway inhibition poses a significant clinical challenge. Here, we report that NUAK family kinase 2 (NUAK2) is an actionable therapeutic target in NEPC. NUAK2 expression is markedly elevated in NEPC patient specimens and preclinical models, and its genetic or pharmacologic inhibition suppresses NEPC tumor growth. The FDA-approved CDK4/6 inhibitor trilaciclib exerts potent inhibition of NUAK2, leading to marked tumor suppression alone and enhanced efficacy in combination with carboplatin. Integrated phosphor-target and interactome analyses demonstrate that NUAK2 engages core spliceosome compon

SUBMITTER: Mehraj U 

PROVIDER: S-EPMC12642401 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature