Non-Viral RNA Therapies for Non-Small Cell Lung Cancer and Their Corresponding Clinical Trials

Ribonucleic acid (RNA)-based therapies represent a promising class of drugs for the treatment of non-small cell lung cancer (NSCLC) due to their ability to modulate gene expression. Therapies leveraging small interfering RNA (siRNA), messenger RNA (mRNA), microRNA (miRNA), and antisense oligonucleotides (ASOs) offer various advantages over conventional treatments, including the ability to target specific genetic mutations and the potential for personalized medicine approaches. However, the clinical translation of these therapeutics for the treatment of NSCLC faces challenges in delivery due to their immunogenicity, negative charge, and large size, which can be mitigated with delivery platforms. In this review, we provide a description of the pathophysiology of NSCLC and an overview of RNA-based therapeutics, specifically highlighting their potential application in the treatment of NSCLC. We discuss relevant classes of RNA and their therapeutic potential for NSCLC. We then discuss challenges in delivery and non-viral delivery strategies such as lipid- and polymer-based nanoparticles that have been developed to address these issues in preclinical models. Furthermore, we provide a summary table of clinical trials that leverage RNA therapies for NSCLC [which includes their National Clinical Trial (NCT) numbers] to highlight the current progress in NSCLC. We also discuss how these NSCLC therapies can be integrated with existing treatment modalities to enhance their efficacy and improve patient outcomes. Overall, we aim to highlight non-viral strategies that tackle RNA delivery challenges while showcasing RNA's potential as a next-generation therapy for NSCLC treatment.