The Dual Role of Autophagy in Cancer: Mechanisms and Therapeutic Strategies

ABSTRACT Autophagy is an evolutionarily conserved lysosomal degradation pathway that maintains cellular homeostasis by eliminating dysfunctional organelles and protein aggregates. Dysregulated autophagy contributes to pathologies including cancer, where it exhibits a dual context‐dependent role. A comprehensive synthesis integrating molecular mechanisms with stage‐specific functions and therapeutic implications of autophagy in cancer remains lacking. In this review, we provide an overview of the core molecular machinery and regulatory networks governing autophagy, integrating with fundamental principles of cancer pathogenesis. We comprehensively discuss the tumor‐suppressive functions of autophagy during cancer initiation, contrasting these with its tumor‐promoting roles in driving tumor progression and metastasis. Moreover, this review covers current strategies for the therapeutic modulation of autophagy, including both activation and inhibition, with a focus on their applications in cancer therapy through monotherapy and combination approaches. The clinical progress and challenges of autophagy‐targeted drugs such as chloroquine (CQ) and hydroxychloroquine (HCQ) are also discussed. We further discuss the potential of autophagy‐related components as biomarkers in cancer. Taken together, understanding the role of autophagy in cancer not only expands the functional scope of autophagy, but also provides a solid foundation for development of novel preventive and therapeutic strategies against cancer.