Therapeutic Targeting of RNA Splicing in Cancer

Abstract

RNA splicing is a key regulatory step in the proper control of gene expression. It is a highly dynamic process orchestrated by the spliceosome, a macro-molecular machinery that consists of protein and RNA components. The dysregulation of RNA splicing has been observed in many human pathologies ranging from neurodegenerative diseases to cancer. The recent identification of recurrent mutations in the core components of the spliceosome in hematologic malignancies has advanced our knowledge of how splicing alterations contribute to disease pathogenesis. This review article will discuss our current understanding of how aberrant RNA splicing regulation drives tumor initiation and progression. We will also review current therapeutic modalities and highlight emerging technologies designed to target RNA splicing for cancer treatment.

Keywords

• alternative splicing
• splicing factor mutations
• spliceosome inhibitors
• anti-sense oligonucleotides
• immuno-oncology therapies