The dual role of the crosstalk between autophagy and ferroptosis in lung cancer treatment: Advances in mechanisms and therapeutic strategies (Review)

The interaction between autophagy and ferroptosis has resulted in the identification of novel approaches for the treatment of lung cancer (LC). The two processes are closely interconnected via three core regulatory modes: Negative regulation, positive regulation and feedback regulation, thereby forming a complex and context‑dependent regulatory network. Within the context of LC progression, the interaction between autophagy and ferroptosis exhibits a dual role. On one hand, it promotes LC development by enabling cancer cell survival in adverse microenvironments, remodeling metabolic pathways and orchestrating the tumor microenvironment to facilitate immune evasion. On the other hand, it can suppress LC by removing damaged cellular components, inducing ferroptosis, and boosting immune surveillance and clearance of cancer cells. Consequently, therapeutic strategies for LC are continuously evolving. In the field of pharmacotherapy, traditional agents such as chloroquine and its derivatives are being repurposed with subtype‑dependent efficacy, and their antitumor activity can be potentiated via nanoparticle delivery systems. When combined with ferroptosis inducers or other drugs, these agents can augment therapeutic efficacy and surmount drug resistance. Current research and development efforts are focused on small‑molecule compounds that target key nodes in autophagy‑ferroptosis crosstalk. Moreover, combination therapy represents a central focus of research. When combined with chemotherapy, radiotherapy, targeted therapy and immunotherapy, this combination approach shows potential for synergistic efficacy. However, current research faces several challenges, including the complexity of regulatory mechanisms and inter‑individual variability. Most therapeutic strategies remain in the preclinical research phase and the synergistic mechanisms of combination therapies are not yet fully elucidated. Comprehensive investigations into the molecular processes, coupled with the application of multi‑omics technologies, are crucial for clarifying the regulatory network. The development of precise biomarkers, along with the integration of artificial intelligence and big data analytics, is essential to accelerate the advancement of novel drugs and therapeutic strategies, with the ultimate goal of improving the prognosis for patients with LC.