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Autophagy is an evolutionarily conserved catabolic process with multifaceted, context-dependent roles in tumor initiation and progression. 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6948-6979. doi: 10.7150/thno.135134  \nReview  \nIntegrating the hallmarks of cancer into autophagy: a perspective from underlying mechanisms to therapeutic strategies  \nHuidi Liu1\\#, Wei Liu2\\#, Xiaochun Zhang3\\#, Yufeng Jiang4, Heng Xu2, Ningning Wang5􀀍, Bo Liu2􀀍, Na Lin6􀀍  \n1. Department of Anus and Intestine Surgery, The First Hospital of China Medical University, Shenyang 110001, China.  \n2. Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.  \n3. Department of Respiratory and Critical Care Medicine, The First Hospital of China Medical University, Shenyang 110001, China.  \n4. Department of Emergency, The First Hospital of China Medical University, Shenyang 110001, China.  \n5. Department of Gastroenterology, The First Hospital of China Medical University, Shenyang 110001, China.  \n6. Department of Hematology, The First Hospital of China Medical University, Shenyang 110001, China.  \n\\#These authors contributed equally to this work.  \n􀀍 Corresponding authors: Ningning Wang, Email: [87k016328@sina.com](87k016328@sina.com); Bo Liu, Email: [liubo2400@163.com](liubo2400@163.com); Na Lin, Email: [salinaofcmu@163.com](salinaofcmu@163.com).  \n© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions.  \nReceived: 2026.03.26; Accepted: 2026.05.06; Published: 2026.05.18  \nAbstract  \n\n| 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. |  |\n| --- | --- |\n| Keywords: autophagy; cancer hallmarks; autophagy modulators; crosstalk; target therapy; molecular mechanism\u003Cbr>Introduction |  |\n| Cancer remains a profound global health crisis and a formidable economic burden, with forecasts suggesting that this challenge will escalate significantly in the years ahead [1] . While substantial progress has undeniably been made in developing cancer treatments, significant hurdles continue to impede consistently successful therapeutic outcomes. A key factor complicating treatment is the intrinsic heterogeneity of the cancer itself [2] . Tumorigenesis is a multistep process driven by cumulative genetic alterations that transform normal human cell","cbCaig1EmQZ9SZ6V","https://ap.wps.com/l/cbCaig1EmQZ9SZ6V","pdf",9339163,32,"English","# Abstract\n# Keywords\n# Introduction\n## Cancer heterogeneity and treatment challenges\n## Origin and expansion of the cancer hallmarks framework\n## Autophagy as a context-dependent process in malignancy","[{\"question\":\"Why do current cancer therapies still show limited clinical outcomes?\",\"answer\":\"Clinical outcomes remain limited by drug resistance, metastasis, and off-target effects arising from tumor complexity and heterogeneity.\"},{\"question\":\"How does the “hallmarks of cancer” framework relate to therapeutic target discovery?\",\"answer\":\"It provides a systematic framework to understand tumor biology and identify therapeutic targets, though hallmark dependencies differ among cancer types.\"},{\"question\":\"What is the review’s central perspective on autophagy and cancer hallmarks?\",\"answer\":\"It summarizes how autophagy is regulated, how it impacts key signaling pathways, categorizes 14 cancer hallmarks into four groups, and discusses crosstalk between autophagy and these hallmarks to inform precision oncology strategies.\"}]","Integrating the hallmarks of cancer into autophagy - a perspective from underlying mechanisms to therapeutic strategies | PDF",1790102695,81]