Autophagy in colorectal cancer: Current understanding of mechanisms and future therapeutic directions

Abstract

Colorectal cancer (CRC) ranks among the most prevalent malignancies globally, distinguished by its high incidence, significant mortality, and poor prognosis. Despite advancements in early screening and therapeutic strategies, clinical outcomes remain suboptimal. In recent years, autophagy has emerged as a pivotal focus in CRC research. Although numerous studies have explored the potential roles of autophagy in CRC, a comprehensive review of recent advances—especially regarding novel autophagy-targeting agents and their underlying mechanisms—remains limited. This review synthesizes recent literature elucidating the role of autophagy in CRC initiation and progression, with a focus on its diagnostic, therapeutic, and prognostic implications. In addition, we highlighted the ongoing controversies surrounding autophagy in CRC research, examined its dual-edged role in therapeutic contexts, and provided an in-depth discussion on leveraging autophagy modulators to block CRC progression. We critically examine current autophagy-based treatment modalities, highlight ongoing controversies, and outline future directions, including personalized autophagy modulation, the development of next-generation autophagy regulators, and cross-disciplinary research opportunities in CRC.