Integrating the hallmarks of cancer into autophagy: a perspective from underlying mechanisms to therapeutic strategies.

Despite remarkable advances in cancer therapy, clinical outcomes remain limited by drug resistance, metastasis, and off-target effects that stem from the complexity and heterogeneity of tumors. The "hallmarks of cancer" provides a systematic framework for understanding tumor biology and identifying therapeutic targets. However, the expression patterns and mechanistic dependencies of these hallmarks differ markedly among cancer types. Autophagy is an evolutionarily conserved catabolic process, exerting multifaceted and context-dependent functions in tumor initiation and malignant progression. In this review, we summarize current insights into the regulation of autophagy and its impact on key signaling pathways. Most importantly, based on the characteristics of tumor progression, we classified the 14 hallmarks of cancer into four categories and discussed the crosstalk between autophagy and these hallmarks. In addition, we survey recent progress in the discovery of small-molecule compounds targeting autophagy and evaluate their therapeutic implications from a hallmark-oriented perspective. Finally, this review highlight that integrating the conceptual framework of cancer hallmarks with the biological and pharmacological functions of autophagy offers a promising avenue for precision oncology. Elucidating how autophagy differentially modulates distinct hallmarks, as synthesized in this review, will be instrumental in facilitating context-specific interventions and guiding future strategies for personalized cancer therapy.