Olazábal-Morán Manuel, Pérez Elena, Esteban-Arranz Adrián, Garrido Antonio
Nanocaging Research Group, Department of Biosciences, School of Biomedical and Health Sciences, Universidad Europea de Madrid, Villaviciosa de Odón, 28670 Madrid, Spain.
Nanocaging Research Group, Department of Pharmacy and Nutrition, School of Biomedical and Health Sciences, Universidad Europea de Madrid, Villaviciosa de Odón, 28670 Madrid, Spain.
Biomolecules. 2025 Sep 13;15(9):1316. doi: 10.3390/biom15091316.
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.
肺癌仍然是全球主要的死亡原因，这是由烟草使用增加、工业化和空气污染所驱动的。尽管在诊断和治疗方面取得了进展，但仍然缺乏有效的治疗方法。活性氧（ROS）在癌症发展中发挥着双重作用，调节关键信号通路并激活细胞死亡通路，使其成为新药的一个有前景的靶点。研究表明，约占肺恶性肿瘤60%的野生型NRF2/KEAP1肺肿瘤对ROS诱导敏感，而突变的肺肿瘤表现出高ROS水平。蛋白水解靶向嵌合体（PROTACs）已成为癌症治疗中替代小分子抑制剂（SMIs）的一种有前景的选择，解决了诸如不可成药和耐药性等局限性。然而，这些面临着诸如细胞穿透有限和潜在毒副作用等挑战。纳米技术引入了“纳米PROTACs”，增强了组织蓄积、膜通透性和控释。在本综述中，将总结ROS在肺癌中的关键作用。此外，将设计一种针对野生型NRF2肿瘤的潜在治疗方法，涉及递送ROS诱导剂纳米PROTAC。这种潜在治疗方法可能为具有这些遗传特征的肺癌患者提供一种潜在的治疗策略。
