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ASCO Educational BookOvercoming KRAS-Mutant Lung Cancer

This comprehensive review highlights the history of discovering RAS and the decades of studies targeting KRAS-driven lung cancer, to the present applications. Although KRAS inhibitors have 36%–45% objective response rates with a median duration of response of 10 months, many tumors do not respond, and a variety of mechanisms of resistance have been observed, including new KRAS alterations, activation of alternate RTK pathway proteins, bypass pathways, and transcriptional remodeling. The authors conclude with a discussion of ongoing clinical trials aimed at overcoming resistance to KRAS inhibitors.