Nucleic Acid-Based Approaches to Tackle KRAS Mutant Cancers

Abstract

Activating mutations in KRAS are highly relevant to various cancers, driving persistent efforts toward the development of drugs that can effectively inhibit KRAS activity. Previously, KRAS was considered ‘undruggable’; however, the recent advances in our understanding of RNA and nucleic acid chemistry and delivery formulations have sparked a paradigm shift in the approach to KRAS inhibition. We are currently witnessing a large wave of next-generation drugs for KRAS mutant cancers—nucleic acid-based therapeutics. In this review, we discuss the current progress in targeting KRAS mutant tumors and outline significant developments in nucleic acid-based strategies. We delve into their mechanisms of action, address existing challenges, and offer insights into the current clinical trial status of these approaches. We aim to provide a thorough understanding of the potential of nucleic acid-based strategies in the field of KRAS mutant cancer therapeutics.