尽管癌症治疗取得了进步，结直肠癌（CRC）仍然是全球死亡的主要原因。自噬是一种进化上保守的溶酶体依赖性降解途径，对于维持细胞稳态至关重要。然而，在癌症中，自噬在预防早期肿瘤形成与维持晚期肿瘤方面可能具有相互冲突的功能。有缺陷的自噬不仅对癌细胞有广泛而动态的影响，而且对影响肿瘤进展和治疗反应的肿瘤微环境也有影响。更复杂的是，CRC 中的体细胞突变包括肿瘤蛋白 p53 (TP53)、v-raf 鼠肉瘤病毒癌基因同源物 B1 (BRAF)、Kirsten 大鼠肉瘤病毒癌基因同源物 (KRAS) 以及磷酸酶和张力蛋白同源物 (PTEN) ）可以通过自噬促进促生存优势，从而产生化疗耐药性。最近的研究还报道了与自噬相关的细胞死亡，其与经典自噬不同，通过使用自噬机制的一部分，这影响了癌症治疗中自噬调节的策略。本文讨论了结直肠癌演变中自噬的分子过程及其在肿瘤微环境中的作用，以及基于自噬抑制或促进的前瞻性治疗方法。它还重点介绍了使用自噬调节剂治疗 CRC 的临床试验，强调了自噬调节在 CRC 治疗中的重要性。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Colorectal cancer (CRC) remains a leading cause of death globally despite the improvements in cancer treatment. Autophagy is an evolutionarily conserved lysosomal-dependent degradation pathway that is critical in maintaining cellular homeostasis. However, in cancer, autophagy may have conflicting functions in preventing early tumour formation versus the maintenance of advanced-stage tumours. Defective autophagy has a broad and dynamic effect not just on cancer cells, but also on the tumour microenvironment which influences tumour progression and response to treatment. To add to the layer of complexity, somatic mutations in CRC including tumour protein p53 (TP53), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), Kirsten rat sarcoma viral oncogene homolog (KRAS), and phosphatase and tensin homolog (PTEN) can render chemoresistance by promoting a pro-survival advantage through autophagy. Recent studies have also reported autophagy-related cell deaths that are distinct from classical autophagy by employing parts of the autophagic machinery, which impacts strategies for autophagy regulation in cancer therapy. This review discusses the molecular processes of autophagy in the evolution of CRC and its role in the tumour microenvironment, as well as prospective therapeutic methods based on autophagy suppression or promotion. It also highlights clinical trials using autophagy modulators for treating CRC, underscoring the importance of autophagy regulation in CRC therapy.Copyright © 2024 Elsevier Inc. All rights reserved.