Recent Advances in Targeting RNA Splicing Factors with Small Molecules.

Pre-mRNA splicing is a process of removing introns from precursor RNA and joining exons to form mature RNA for protein translation. The processes are classified into constitutive and alternative splicing, with which multiple mRNA transcripts are generated from a single coding gene to expand protein diversity. Frequent mutations or abnormal expressions of some splicing factors dysregulate splicing in a subset of transcripts, leading to aberrant gene expression patterns. Notable splicing factors, including SF3B1, U2AF1, SRSF2, and RBM39, are considered potential drug targets for various cancers. Advancement in the discovery and development of small molecules targeting specific splicing factors has become a new treatment modality for cancer therapy. Here, we review recurrent mutations and dysregulated expressions of splicing factors in cancers and provide our perspective on recent developments of small-molecule compounds targeting splicing factors and the functional assays that facilitate hit/lead discovery for development to treat cancer.