Multi-omics approach to identifying isoform variants as therapeutic targets in cancer patients

Abstract

Cancer-specific alternatively spliced events (ASE) play a role in cancer pathogenesis and can be targeted by immunotherapy, oligonucleotide therapy, and small molecule inhibition. However, identifying actionable ASE targets remains challenging due to the uncertainty of its protein product, structure impact, and proteoform (protein isoform) function. Here we argue that an integrated multi-omics profiling strategy can overcome these challenges, allowing us to mine this untapped source of targets for therapeutic development. In this review, we will provide an overview of current multi-omics strategies in characterizing ASEs by utilizing the transcriptome, proteome, and state-of-art algorithms for protein structure prediction. We will discuss limitations and knowledge gaps associated with each technology and informatics analytics. Finally, we will discuss future directions that will enable the full integration of multi-omics data for ASE target discovery.

Non-coding RNAs regulate mitochondrial dynamics in the development of gastric cancer

“…Some studies have shown that RNA-based therapies have good clinical potential because RNA can directly target specific genes and their products ( Lin et al, 2020 ; Wu et al, 2022 ). At present, some RNA-based therapies approved worldwide target specific genes in liver or muscle cells and change gene expression by injecting siRNA or oligonucleotide chains ( Shaw et al, 2022 ). Since the important role of ncRNAs in GC progression has been fully demonstrated, they are becoming a new class of targets for RNA-based drug discovery.…”

RNA-binding proteins regulating the CD44 alternative splicing

“…Thus, CD44 is a family of transmembrane glycoproteins with a high heterogeneity in molecular weight . Alternative splicing (AS) is often deregulated in cancer, and cancer-specific isoform switches are part of the oncogenic transformation of cells (Di et al, 2018;Zhang et al, 2021;Shaw et al, 2022;Bradley and Anczuków, 2023). Indeed, accumulating evidence supports the concept that CD44 isoforms play different roles in cancer cells as compared to their normal counterparts (Zöller, 2011;Bhattacharya et al, 2018;Xu et al, 2020).…”