{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:59:09Z","timestamp":1791896349674,"version":"4.3.4"},"reference-count":66,"publisher":"Harborside Press, LLC","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>\n                    <jats:italic>KRAS<\/jats:italic>\n                    mutations are the most common oncogenic driver alterations in non\u2013small cell lung cancer (NSCLC) and define biologically heterogeneous diseases shaped by mutation subtype, co-mutation patterns, and immune contexture. Recent advances in structural and chemical biology have transformed\n                    <jats:italic>KRAS<\/jats:italic>\n                    from an undruggable target into a rapidly expanding therapeutic vulnerability. The first allele-specific inhibitors, sotorasib and adagrasib, validated\n                    <jats:italic>KRAS<\/jats:italic>\n                    <jats:sup>G12C<\/jats:sup>\n                    as a druggable dependency, changing the treatment paradigm for previously treated\n                    <jats:italic>KRAS<\/jats:italic>\n                    <jats:sup>G12C<\/jats:sup>\n                    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\n                    <jats:italic>KRAS<\/jats:italic>\n                    alterations, bypass receptor tyrosine kinase (RTK) signaling, and adaptive MAPK reactivation. These challenges have spurred the development of KRAS(ON) inhibitors, dual ON\/OFF inhibitors, and broader pan-\n                    <jats:italic>KRAS<\/jats:italic>\n                    and pan-\n                    <jats:italic>RAS<\/jats:italic>\n                    agents capable of targeting multiple oncogenic variants, including G12D, G12V, G12X, G13X, and Q61X. 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\u2013MEK clamps, adoptive cell therapies, and\n                    <jats:italic>KRAS<\/jats:italic>\n                    vaccines, are broadening the therapeutic landscape. This review comprehensively summarizes\n                    <jats:italic>KRAS<\/jats:italic>\n                    biology, therapeutic advances, mechanisms of resistance, and emerging strategies that are reshaping the treatment landscape of\n                    <jats:italic>KRAS<\/jats:italic>\n                    -mutant NSCLC.\n                  <\/jats:p>","DOI":"10.6004\/jnccn.2026.7038","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:56:51Z","timestamp":1789739811000},"source":"Crossref","is-referenced-by-count":0,"title":["Targeting KRAS-Mutant Lung Cancers"],"prefix":"10.6004","volume":"24","author":[{"given":"Edoardo","family":"Garbo","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Department of Oncology, University of Torino, S. Luigi Gonzaga Hospital, Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Scaparone","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Jing","family":"Hoe","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice T.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Ambrogio","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino, Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biagio","family":"Ricciuti","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"B1","series-title":"Crit Rev Oncol Hematol","first-page":"104554","article-title":"KRAS mutations in advanced non-small cell lung cancer: from biology to novel therapeutic strategies","volume":"205","author":"Liguori L","year":"2025","unstructured":"Liguori L, Salomone F, Viggiano A,  KRAS mutations in advanced non-small cell lung cancer: from biology to novel therapeutic strategies. 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