Alternative Splicing in Lung Adenocarcinoma: From Bench to Bedside

Lung adenocarcinoma (LUAD) is a highly heterogeneous tumor and the most prevalent pathological type of lung cancer. The alternative splicing (AS) of mRNA enables the generation of multiple protein products from a single gene. This is a tightly regulated process that significantly contributes to the proteome diversity in eukaryotes. Recent multi-omics studies have delineated the splicing profiles that underline LUAD tumorigenesis from initiation to metastasis. Such progress holds robust promise to facilitate the development of screening strategies and individualized therapies. Perturbed AS fosters the emergence of novel neoantigen resources and disturbances in the immune microenvironment, which allow new investigations into modulatory targets for LUAD immunotherapy. This review presents an update on the landscape of dysregulated splicing events in LUAD and the associated mechanisms and theranostic perspectives with unique insights into AS-based immunotherapy, such as Chimeric Antigen Receptor T cell therapy. These AS variants can be used in conjunction with current therapeutic modules in LUAD, allowing bench to bedside translation to combat this highly malignant cancer.