The potential of peptide-based inhibitors in disrupting protein–protein interactions for targeted cancer therapy

Abstract

Protein-protein interactions (PPIs) form an intricate cellular network known as the interactome, which is essential for various cellular processes, such as gene regulation, signal transduction, and metabolic pathways. The dysregulation of this network has been closely linked to various disease states. In cancer, these aberrant PPIs, termed oncogenic PPIs (OncoPPIs), are involved in tumour formation and proliferation. Therefore, the inhibition of OncoPPIs becomes a strategy for targeted cancer therapy. Small molecule inhibitors have been the dominant strategy for PPI inhibition owing to their small size and ability to cross cell membranes. However, peptide-based inhibitors have emerged as compelling alternatives, offering distinct advantages over small molecule inhibitors. Peptides, with their larger size and flexible backbones, can effectively engage with the broad interfaces of PPIs. Their high specificity, lower toxicity, and ease of modification make them promising candidates for targeted cancer therapy. Over the past decade, significant advancements have been made in developing peptide-based inhibitors. This review discusses the critical aspects of targeting PPIs, emphasizes the significance of OncoPPIs in cancer therapy, and explores the advantages of using peptide-based inhibitors as therapeutic agents. It also highlights recent progress in peptide design aimed at overcoming the limitations of peptide therapeutics, offering a comprehensive overview of the current landscape and potential of peptide-based inhibitors in cancer treatment.