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Targeting autophagy in oral squamous cell carcinoma chemoresistance: molecular mechanisms, therapeutic strategies, and emerging nanotherapeutic approaches.

Created on 29 Jul 2026

Authors

Han Su, Jianlei He, Wenyi Xu, Guijuan Feng, Ke Xu

Published in

Molecular biology reports. Volume 53. Issue 1. Jul 29, 2026. Epub Jul 29, 2026.

Abstract

Autophagy is a lysosome-dependent recycling process that maintains cellular homeostasis and helps cells adapt to therapeutic stress. In oral squamous cell carcinoma (OSCC), dysregulated autophagy may promote chemoresistance by supporting metabolic adaptation, removing damaged cellular components, and limiting treatment-induced cell death. Its effects are nevertheless context dependent, as autophagy can also interact with apoptosis, ferroptosis, and other cytotoxic pathways. This review summarizes molecular mechanisms linking autophagy to OSCC chemoresistance, focusing on non-coding RNAs, p53/TP53, BECN1, ATG-related proteins, oncogenic signaling networks, and emerging biomolecular-condensate mechanisms. It also evaluates therapeutic strategies, including early- and late-stage autophagy inhibition, mTOR-targeted modulation, metabolic interventions, genetic approaches for mechanistic validation, ferroptosis-autophagy combinations, and nanotechnology-assisted delivery systems. Although promising effects have been reported in cell lines, drug-resistant derivatives, cancer stem cell-like populations, and xenograft models, OSCC-specific clinical evidence remains limited. Future progress will require rigorous assessment of autophagic flux, careful interpretation of related head and neck squamous cell carcinoma evidence, biomarker-guided patient stratification, and validation in clinically relevant models. Integrating autophagy biology with molecular stratification and rational combination therapy may help overcome chemoresistance in OSCC.

PMID:
42525293
Bibliographic data and abstract were imported from PubMed on 29 Jul 2026.

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