Autophagy Modulation in Cancer Therapy: Navigating the Dual Roles to Overcome Chemoresistance
Md Mohiuddin1, Md Al Mamun Ahsan2
1Department of Pharmacy Southeast University Dhaka Bangladesh.
Health Science Reports
|July 28, 2026
Summary
Autophagy plays a dual role in cancer, acting as both a tumor suppressor and a promoter of cancer cell survival. Targeting autophagy selectively, rather than globally, is key to overcoming chemoresistance and improving cancer treatment outcomes.
Area of Science:
- Cellular Biology
- Oncology
- Pharmacology
Background:
- Autophagy, a cellular recycling process, exhibits complex roles in cancer, acting as both a tumor suppressor and a pro-survival mechanism.
- This duality complicates therapeutic strategies aimed at overcoming chemoresistance, a significant clinical challenge.
- Autophagy's function is highly context-dependent, varying with tumor stage, cellular heterogeneity, and the tumor microenvironment.
Purpose of the Study:
- To examine the multifaceted role of autophagy in cancer.
- To explore therapeutic modulation of autophagy for enhancing chemosensitivity.
- To discuss the limitations of current autophagy inhibitors and the potential of selective autophagy targeting.
Main Methods:
- Review of current literature on autophagy in cancer.
- Critical analysis of first-generation autophagy inhibitors (e.g., hydroxychloroquine, chloroquine).
- Emphasis on emerging selective autophagy pathways (mitophagy, ER-phagy) and their therapeutic implications.
Main Results:
- First-generation autophagy inhibitors lack specificity and can cause off-target toxicities.
- Selective autophagy pathways show context-dependent impacts on therapeutic outcomes.
- Successful autophagy-targeted therapy necessitates a precision-based approach considering tumor heterogeneity and microenvironment.
Conclusions:
- Targeting autophagy for chemoresistance requires a shift from global modulation to selective, context-specific interventions.
- Future research should focus on developing selective autophagy modulators and predictive biomarkers.
- Integrating nanomedicine for spatiotemporal control is crucial for optimizing autophagy-targeted cancer therapy.
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