High cereblon expression in neuroendocrine cancer confers vulnerability to GSPT1 molecular glue degrader.

ABSTRACT:

Background

Recent advances in targeted therapies have introduced molecular glue degraders (MGDs) that leverage the cereblon (CRBN) E3 ubiquitin ligase to degrade the translation termination factor GSPT1. Understanding the cellular context for the selective targeting of cancer cells by GSPT1 MGDs is crucial.

Methods

This study investigated the sensitivity of neuroendocrine cancer (NEC) cells to GSPT1MGDs across a pan-cancer cell line panel, examining the correlation between therapeutic response and cellular characteristics such as CRBN expression and neuroendocrine (NE) marker levels. The role of CRBN in enhancing MGD sensitivity was further validated through CRBN overexpression and NEC-driving factor expression experiments in non-NEC and lung adenocarcinoma cells. The sensit

SUBMITTER: Park J 

PROVIDER: S-EPMC12186427 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature