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Updated: Aug 28, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Overcoming mTOR Inhibitor Resistance: From Biological Basis to Therapeutic Strategies
Xi-Feng Jin1, Ling Liu1, Jun-Jun Zhang1
1Departments of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
Abstract:
Resistance to mTOR inhibition is mediated by multiple adaptive mechanisms, including feedback activation of the PI3K/AKT/mTOR pathway, autophagic adaptation, metabolic reprogramming, immune evasion, tumor heterogeneity, and microenvironmental crosstalk. Recent research has also elucidated the crucial role of RNA modifications, particularly m6A methylation, and the regulatory impact of non-coding RNAs in facilitating tumor adaptation to mTOR blockade. Accordingly, novel therapeutic approaches are emerging. The combination of PI3K/AKT/mTOR inhibitors with immune checkpoint blockades represents a promising strategy for overcoming therapeutic resistance. Additionally, next-generation mTOR inhibitors and synthetic lethality strategies are being tailored to target specific tumor profiles. Furthermore, advancements in multi-omics technologies and AI-powered predictive models are transforming personalized cancer treatment. This comprehensive review delves into the molecular intricacies of mTOR inhibitor resistance and explores innovative strategies aimed at enhancing therapeutic outcomes and improving patient responses.
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