RNA-binding proteins as therapeutic targets in cancer

Abstract

RNA-binding proteins (RBPs) have emerged as critical regulators of cancer progression, influencing virtually all hallmarks of cancer. Their ability to modulate gene expression patterns that promote or inhibit tumorigenesis has positioned RBPs as promising targets for novel anti-cancer therapies. This mini-review summarizes the current state of RBP-targeted cancer treatments, focusing on five examples, eIF4F, FTO, SF3B1, RBM39 and nucleolin. We highlight the diversity of current targeting approaches and discuss ongoing challenges including the complexity of RBP regulatory networks, potential off-target effects and the need for more specific targeting methods. By assessing the future potential of novel therapeutic avenues, we provide insights into the evolving landscape of cancer treatment and the critical role RBPs may play in next-generation therapeutics.

Keywords: ASO; RNA-binding proteins; SMI; aptamer; cancer; molecular glue; therapeutic targets.

Figure 1.

Therapeutic targeting of oncogenic RBPs. The figure illustrates the function of key RBPs (eIF4F, FTO, SF3B1, RBM39 and nucleolin) at various stages of the RNA life cycle (yellow boxes) and their respective inhibitors (red). Proteins are not drawn to scale. (1) eIF4F: Antisense oligonucleotides (ASOs) and small molecule inhibitors (SMIs) against different components of eIF4F reduce target mRNA translation. (2) FTO: SMIs bind to the catalytic pocket of FTO inhibiting RNA demethylation. (3) SF3B1: SMIs promote aberrant splicing, especially of transcripts containing weak branch points. (4) RBM39: Molecular glues promote the interaction of this factor with the E3 ubiquitin ligase complex, leading to its ubiquitination and subsequent degradation. (5) Nucleolin: aptamers and peptides inhibit this multifunctional protein, affecting several steps of gene expression.