Cancer Biology of GSPT1: Mechanisms and Targeted Therapy Opportunities of Molecular Glue Degraders

  • Adv Sci (Weinh). 2025 Dec;12(47):e11789. doi: 10.1002/advs.202511789.
Qiqi Lin  1 ,  Wenjing Liu  1 ,  Wenjia Lu  2 ,  Monong Zhao  1 ,  Lin Cao  1 ,  Zhiyu Li  3 ,  Jubo Wang  3 ,  Xi Xu  3 ,  Hongxi Wu  1
Affiliations
  • 1. State Key Laboratory of Natural Medicines, Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
  • 2. School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, 211198, China.
  • 3. State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
PMID: 41194439 DOI: 10.1002/advs.202511789
Abstract

G1 to S phase transition protein (GSPT1), a small GTPase involved in translation termination, which promotes the progression of Cancer cells, has emerged as an attractive potential therapeutic target for Cancer treatment with the rapid breakthrough of molecular glue degraders (MGDs). Although the precise mechanism of GSPT1 in Cancer biology is partially understood, in this review, the characteristics of GSPT1 expression and regulatory networks are systematically attempted to be addressed, from insights into the structure, expression, and molecular mechanisms, highlighting the distribution and isoform-specific signaling of GSPT1 in tumors. The clinical significance is emphasized, immune interactions, and oncogenic pathways of GSPT1-targeted therapies, proposing strategies to address current challenges and provide therapeutic opportunities for the application of GSPT1 degraders in precision oncology. A novel future direction is hoped to provide to enhance the treatment response of GSPT1 MGDs in clinical implications.

Keywords
GSPT1; cancer biological function; molecular glue degrader; precision oncology; translation termination.
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