The neuroendocrine transition in prostate cancer is dynamic and dependent on ASCL1.

ABSTRACT: Lineage plasticity is a hallmark of cancer progression that impacts therapy outcomes, yet the mechanisms mediating this process remain unclear. Here, we introduce a versatile in vivo platform to interrogate neuroendocrine lineage transformation throughout prostate cancer progression. Transplanted mouse prostate organoids with human-relevant driver mutations (Rb1^-/-; Trp53^-/-; cMyc⁺ or Pten^-/-; Trp53^-/-; cMyc⁺) develop adenocarcinomas, but only those with Rb1 deletion advance to aggressive, ASCL1⁺ neuroendocrine prostate cancer (NEPC) resistant to androgen receptor signaling inhibitors. Notably, this transition requires an in vivo microenvironment not replicated by conventional organoid culture. Using multiplexed i

SUBMITTER: Romero R 

PROVIDER: S-EPMC11584404 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature