Advancements in Sotorasib: A Comprehensive Review of its Efficacy in Non-small Lung Cancer Treatment.

Sotorasib (SR), a first-in-class KRAS G12C inhibitor developed by Amgen, represents a major advancement in the treatment of non-small cell lung cancer (NSCLC) with KRAS G12C mutations. This comprehensive review covers the drug's development, mechanism of action, pharmacokinetics, synthesis, and analytical methods. KRAS mutations, particularly KRAS G12C, are associated with poor prognosis in NSCLC, with approximately 13% of cases harboring this mutation. SR targets the KRAS G12C mutation by covalently binding to the cysteine residue in the KRAS protein, inhibiting its signalling pathways and promoting tumour cell death. Approved by the FDA in 2021, SR has demonstrated promising efficacy, including significant objective response rates and progression-free survival benefits in pretreated patients with NSCLC. The development of resistance mechanisms, such as secondary mutations and alternative signalling pathways, remains a challenge, underscoring the need for ongoing research into combination therapies and further trials. This review also highlights the drug's synthetic processes, structural features, and global patent coverage. SR approval marks a significant milestone in KRAS-targeted therapies, offering new hope for patients with difficult-to-treat lung cancer.