The Expanding Functional Landscape of GSTP1 in Cancer Beyond Detoxification.

Authors

Wanyu Chen, Yuchen Jiang, Zhi-Jie Xiao

Published in

Critical reviews in oncology/hematology. Pages 105568. Aug 26, 2026. Epub Aug 26, 2026.

Abstract

Glutathione S-transferase P1 (GSTP1), a canonical phase II detoxification enzyme, has long been recognized for its role in drug resistance via glutathione (GSH)-mediated conjugation and clearance of chemotherapeutic agents. However, accumulating evidence has uncovered its multifaceted non-canonical functions that critically contribute to cancer progression beyond detoxification. This review systematically synthesizes the latest advances in understanding GSTP1's divergent roles in cancer biology, including regulation of oncogenic signaling pathways, maintenance of redox homeostasis, modulation of metabolic reprogramming, and shaping of the tumor immune microenvironment. GSTP1 also plays important roles in key cancer hallmarks including tumorigenesis, metastasis, cancer stemness maintenance, and resistance to chemotherapy, targeted therapy, radiotherapy, and immunotherapy. Clinically, GSTP1 promoter hypermethylation serves as a valuable epigenetic biomarker for cancer diagnosis, prognosis stratification, and therapeutic response prediction via liquid biopsy. Furthermore, the development of GSTP1-targeted inhibitors, either as monotherapy or in combination with other anticancer modalities, has shown promising preclinical efficacy in overcoming treatment resistance. Despite these advances, critical questions remain regarding the precise molecular mechanisms underlying GSTP1's nuclear functions, its context-dependent roles (oncogenic versus tumor-suppressive), and the translation of targeted therapies to clinical practice. Future research focusing on these unresolved areas will deepen our understanding of GSTP1's complex biology and facilitate the development of novel personalized therapeutic strategies for cancer therapy.

PMID:
42648416
Bibliographic data and abstract were imported from PubMed on 27 Aug 2026.

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