Autophagy and radiotherapy in esophageal cancer: modulating treatment sensitivity and overcoming challenges

Esophageal cancer (ESCA) is one of the most fatal gastrointestinal cancers worldwide. ESCA is often diagnosed in its middle or late stages since the first symptoms are not identifiable. The use of radiotherapy, either alone or in conjunction with surgical intervention and chemotherapy, is essential to achieve a positive prognosis. Radiotherapy is an essential component of treatment for ESCA. Autophagy, a prevalent biological phenomenon, has a twofold impact on the incidence, progression, and treatment response of malignant tumors. This review explores the intricate mechanisms by which autophagy modulates radiation sensitivity in ESCA, including its effects on DNA repair, oxidative stress responses, and apoptosis. We provide a comprehensive analysis of recent advancements in the modulation of autophagy, focusing on the use of autophagy inhibitors and inducers to enhance radiotherapy efficacy. We discuss how autophagy inhibitors such as chloroquine and 3-methyladenine can overcome radiation resistance by blocking autophagic processes, while autophagy inducers like rapamycin can sensitize cancer cells to radiotherapy-induced cell death. Additionally, we examine the potential therapeutic benefits of combining autophagy regulation with existing treatment modalities, offering new strategies to improve patient outcomes. This review highlights the critical role of autophagy in ESCA and underscores the promise of autophagy-targeted therapies in enhancing the effectiveness of radiotherapy, thereby providing a novel avenue for overcoming treatment resistance and improving prognosis in ESCA patients.