Targeting KRAS-Mutant Lung Cancers. (PubMed, J Natl Compr Canc Netw) - Sep 19, 2026 - "The first allele-specific inhibitors, sotorasib and adagrasib, validated KRASG12C as a druggable dependency, changing the treatment paradigm for previously treated KRASG12C NSCLC, although primary, acquired, and adaptive resistance remain widespread. Next-generation inhibitors such as divarasib improve potency and tolerability but continue to face resistance through secondary KRAS alterations, bypass receptor tyrosine kinase (RTK) signaling, and adaptive MAPK reactivation...Early clinical results with tricomplex RAS(ON) inhibitors (eg, daraxonrasib) and G12D-selective agents (eg, zoldonrasib) demonstrate promising activity in subsets historically lacking targeted options. In parallel, rational combination strategies aimed at enhancing overall efficacy, such as RTK, SHP2/SOS1, or PD-1/PD-L1 blockade, together with emerging modalities including RAF-MEK clamps, adoptive cell therapies, and KRAS vaccines, are broadening the therapeutic landscape. This review..."
IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS
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Alice T Shaw; Biagio Ricciuti; Chiara Ambrogio; Edoardo Garbo; Hui Jing Hoe; Jia Luo; Pietro Scaparone
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