ArticleOncogene2022
GSTM2 is a key molecular determinant of resistance to SG-ARIs.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Proteomic Analysis Reveals AMPKα-Mediated Antiandrogen Resistance via Ferroptosis Suppression in Prostate Cancer.Cancer science · 2026Article
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- A Bayesian Informative Shrinkage Approach for Large-scale Multiple Hypothesis Testing (BISHOT): with Applications in Differential Analysis of Omics Data.bioRxiv : the preprint server for biology · 2025Article
- Distinct Oxidative Stress Adaptations Driven by the Overexpression of miR-526b, miR-655, and COX-2 in Breast Cancer.International journal of molecular sciences · 2025Article
- Article
- Loss of YTHDF1 suppresses the progression of malignant rhabdoid tumor of the kidney by regulating Glutathione S-transferase Mu 2 (GSTM2).Cell biology and toxicology · 2025Article
- Nuclear mitochondrial acetyl-CoA acetyltransferase 1 orchestrates natural killer cell-dependent antitumor immunity in colorectal cancer.Signal transduction and targeted therapy · 2025Article
- Metformin in overcoming enzalutamide resistance in castration-resistant prostate cancer.The Journal of pharmacology and experimental therapeutics · 2025Article
- PLK1: A Promising Therapeutic Target for Prostate Cancer Treatment.Serican journal of medicine · 2024Article
- GSTM2 alleviates heart failure by inhibiting DNA damage in cardiomyocytes.Cell & bioscience · 2023Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Prostate cancer (PCa) continues to threaten men's health, and treatment targeting the androgen receptor (AR) pathway is the major therapy for PCa patients. Several second-generation androgen receptor inhibitors (SG-ARIs), including enzalutamide (ENZ), apalutamide (APA) and darolutamide (DARO), have been developed to better block the activity of AR. Unavoidably, emergence of resistance to these novel drugs still persists. Herein, we identified glutathione S-transferase Mu 2 (GSTM2) as an important determinant in the acquisition of resistance to SG-ARIs. Elevated GSTM2 was detected in enzalutamide-resistant (ENZ-R) PCa, and overexpression of GSTM2 in naïve enzalutamide-sensitive (ENZ-S) cells effectively transformed them to ENZ-R PCa. Aryl hydrocarbon receptor (AhR), the upstream transcription factor, was implicated in the overexpression of GSTM2 in ENZ-R cells. Mechanistically, GSTM2 antagonized the effect of ENZ by rescuing cells from oxidative stress-associated damage and activation of p38 MAPK pathway. Surprisingly, high GSTM2 levels also associated with cross-resistance to APA and DARO. Taking together, these results provide new insight to ameliorate resistance to SG-ARIs and improve treatment outcome.
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