The Role of Reactive Oxygen Species in Lung Cancer Development: Nanomedicine as a Therapeutic Strategy.

Lung cancer remains a leading cause of mortality worldwide, driven by increased tobacco use, industrialization, and air pollution. Despite advancements in diagnostics and treatments, effective therapies are still lacking. Reactive oxygen species (ROS) play a dual role in cancer development, regulating key signaling pathways and activating cell death pathways, making them a promising target for new drugs. Research shows that wild-type NRF2/KEAP1 lung tumors, which account for about 60% of lung malignancies, are sensitive to ROS induction, and mutated lung tumors exhibit high ROS levels. Proteolysis-targeting chimeras (PROTACs) have emerged as a promising alternative to small molecule inhibitors (SMIs) for cancer treatment, addressing limitations like undruggability and drug resistance. However, these face challenges such as limited cell penetration and potential toxic side effects. Nanotechnology has introduced "nano-PROTACs," enhancing tissue accumulation, membrane permeability, and controlled release. In this review, the keystones of ROS in lung cancer will be summarized. Also, a potential therapy for tumors with wild-type NRF2 involving the delivery of ROS inductor nano-PROTAC will be designed. This potential therapy could suppose a potential therapeutic strategy for lung cancer patients with these genetic characteristics.