KRAS-targeted therapies in cancer: novel approaches and overcoming resistance.

ABSTRACT: KRAS, once considered undruggable, has become actionable across specific alleles, with KRAS-G12C inhibitors now approved and next-generation approaches-including pan-KRAS/pan-RAS inhibitors, targeted degraders and RNA-based strategies-progressing rapidly. However, clinical benefit remains limited due to the frequent emergence of resistance. Escape mechanisms include on-target secondary mutations, pathway reactivation, epithelial-mesenchymal transition, lineage plasticity and metabolic rewiring within an immunosuppressive tumour microenvironment. Emerging evidence supports rational combination strategies, including parallel inhibition of epidermal growth factor receptor, protein tyrosine phosphatase non-receptor type 11 or SOS1 and vertical blockade of the mitogen-activated protein kinase-e

SUBMITTER: Tang D 

PROVIDER: S-EPMC12658495 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature