Autophagy and oxidative stress in solid tumors: Mechanisms and therapeutic opportunities

Abstract

Cancer remains a leading cause of mortality worldwide, with solid tumors representing most cases. Autophagy and oxidative stress are two interconnected cellular mechanisms that influence tumor initiation, therapeutic response and disease progression. Autophagy plays a context-dependent role, functioning as a tumor suppressor by eliminating damaged organelles in early stages, while later supporting tumor survival under metabolic and therapeutic stress. Similarly, oxidative stress, characterized by an imbalance in reactive oxygen species (ROS), can drive tumorigenesis by promoting genomic instability and resistance to therapy but can also induce apoptosis in cancer cells. The crosstalk between autophagy and oxidative stress plays a pivotal role in shaping the tumor microenvironment, affecting immune evasion, drug resistance, and metabolic adaptation. Targeting these processes through pharmacological modulation presents both challenges and opportunities in cancer therapy. While autophagy inhibition can enhance chemotherapy efficacy by preventing tumor cell survival mechanisms, excessive oxidative stress induction may lead to cellular damage and systemic toxicity. This review explores the complex interplay between autophagy and oxidative stress in solid tumors, emphasizing their implications for cancer progression and treatment strategies. By understanding these mechanisms, novel therapeutic approaches, including combination therapies and precision medicine strategies, may be developed to improve patient outcomes.