Targeting Oncogenic miRNAs in NSCLC: Therapeutic Strategies and Emerging Approaches

Huimin Su,1 Yuanyuan Zou2 1Department of Internal Medicine II, The Third Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Department of Neurosciences, Mental Health and Sensory Organs — NESMOS, Sapienza University of Rome, Rome, ItalyCorrespondence: Yuanyuan Zou, Department of Neurosciences, Mental Health and Sensory Organs — NESMOS, Sapienza University of Rome, Rome, 00185, Italy, Email yuanyuan.zou@uniroma1.itAbstract: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths globally, with poor prognosis in advanced stages despite therapeutic advances. MicroRNAs (miRNAs) play a critical role in NSCLC pathogenesis, acting as tumor suppressors or oncogenes (oncomiRs), regulating key pathways involved in cancer progression and drug resistance. This review explores various therapeutic strategies targeting oncogenic miRNAs in NSCLC, with a particular focus on small molecule inhibitors (SMIs). SMIs offer potential advantages over RNA-based therapies, such as better pharmacokinetics and oral bioavailability, though direct evidence for SMIs targeting oncogenic miRNAs in NSCLC remains limited. The review examines current research on SMIs, miRNA mimics, antisense oligonucleotides, and other approaches, while discussing the challenges and opportunities for clinical translation. It concludes that while miRNA-based therapies are promising, substantial research is needed to develop effective and selective small molecule inhibitors for NSCLC treatment.Keywords: small molecule, microRNA, NSCLC, exosomes