# Alternative Splicing in Lung Adenocarcinoma: From Bench to Bedside

## TL;DR

This review explores how alternative splicing contributes to lung adenocarcinoma and how it can be used to improve cancer treatments, including immunotherapies like CAR T cell therapy.

## Contribution

The paper provides an updated overview of dysregulated splicing events in lung adenocarcinoma and their therapeutic implications, particularly in immunotherapy.

## Key findings

- Alternative splicing generates proteome diversity and influences lung adenocarcinoma development.
- Dysregulated splicing creates neoantigens that can be targeted by immunotherapies such as CAR T cell therapy.
- AS-based strategies offer potential for individualized therapies and improved screening in lung adenocarcinoma.

## Abstract

Lung adenocarcinoma is the most prevalent pathological type of lung cancer. Alternative splicing generates multiple protein products from a single gene, significantly contributing to proteome diversity. Dysregulated splicing influences the development of lung adenocarcinoma and creates novel neoantigens for current immunotherapies, such as Chimeric Antigen Receptor T cell therapy. This review discusses alternative splicing events and therapeutic strategies, highlighting the potential to enhance anti-cancer treatments for lung adenocarcinoma.

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.