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- Marco H. Hofmann
- 1Discovery Research, Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.
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- Daniel Gerlach
- 1Discovery Research, Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.
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- Sandra Misale
- 2Molecular Pharmacology Program, Memorial Sloan-Kettering Cancer Center, New York, New York.
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- Mark Petronczki
- 1Discovery Research, Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.
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- Norbert Kraut
- 1Discovery Research, Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.
説明
<jats:title>Abstract</jats:title> <jats:sec> <jats:title /> <jats:p>KRAS is the most frequently mutated oncogene, harboring mutations in approximately one in seven cancers. Allele-specific KRASG12C inhibitors are currently changing the treatment paradigm for patients with KRASG12C-mutated non–small cell lung cancer and colorectal cancer. The success of addressing a previously elusive KRAS allele has fueled drug discovery efforts for all KRAS mutants. Pan-KRAS drugs have the potential to address broad patient populations, including KRASG12D-, KRASG12V-, KRASG13D-, KRASG12R-, and KRASG12A-mutant or KRAS wild-type–amplified cancers, as well as cancers with acquired resistance to KRASG12C inhibitors. Here, we review actively pursued allele-specific and pan-KRAS inhibition strategies and their potential utility.</jats:p> </jats:sec> <jats:sec> <jats:title>Significance:</jats:title> <jats:p>Mutant-selective KRASG12C inhibitors target a fraction (approximately 13.6%) of all KRAS-driven cancers. A broad arsenal of KRAS drugs is needed to comprehensively conquer KRAS-driven cancers. Conceptually, we foresee two future classes of KRAS medicines: mutant-selective KRAS drugs targeting individual variant alleles and pan-KRAS therapeutics targeting a broad range of KRAS alterations.</jats:p> </jats:sec>
収録刊行物
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- Cancer Discovery
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Cancer Discovery 12 (4), 924-937, 2022-01-19
American Association for Cancer Research (AACR)