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Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants

2022; American Association for Cancer Research; Volume: 12; Issue: 4 Linguagem: Inglês

10.1158/2159-8290.cd-21-1331

2159-8290

Marco H. Hofmann, Daniel Gerlach, Sandra Misale, Mark Petronczki, Norbert Kraut,

Cancer Genomics and Diagnostics

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.