Authors : Dr. Pasham Uma; Dandotikar Neha; Dr. R. L. Manisha; Muvvala Sudhakar

Volume/Issue : Volume 11 - 2026, Issue 8 - August

Google Scholar : https://tinyurl.com/2vtshsk3

Scribd : https://tinyurl.com/56ckj66a

DOI : https://doi.org/10.38124/ijisrt/26aug015

Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.

Abstract : KRAS is among the most commonly mutated oncogenes in human cancers, driving tumour initiation, progression, and therapeutic resistance through dysregulation of multiple signalling pathways. For many years, KRAS was regarded as an undruggable target because of its high affinity for guanosine nucleotides and the absence of suitable drug-binding pockets. Recent advances in structural biology and medicinal chemistry have fundamentally changed this perspective, enabled the development of mutation-specific inhibitors and established KRAS as a clinically actionable target in precision oncology. The discovery of the switch-II binding pocket facilitated the design of selective covalent inhibitors targeting KRAS G12C, leading to the clinical approval of sotorasib and adagrasib for selected patients with KRAS G12C-mutated malignancies. These breakthroughs have validated direct KRAS inhibition as an effective therapeutic strategy. However, durable clinical responses remain limited by intrinsic and acquired resistance, pathway reactivation, tumour heterogeneity, and the lack of effective therapies for non-G12C KRAS mutations.

Keywords : KRAS; Precision Oncology; Targeted Cancer Therapy; KRAS Inhibitors; Drug Resistance; Cancer Drug Development.

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