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Next batter up! Targeting cancers with KRAS-G12D mutations

2023; Elsevier BV; Volume: 9; Issue: 11 Linguagem: Inglês

10.1016/j.trecan.2023.07.010

2405-8033

Mara N. Zeissig, Lauren M. Ashwood, Olga Kondrashova, Kate D. Sutherland,

Cancer Immunotherapy and Biomarkers

KRAS is the most frequently mutated oncogene in cancer. Activating mutations in codon 12, especially G12D, have the highest prevalence across a range of carcinomas and adenocarcinomas. With inhibitors to KRAS-G12D now entering clinical trials, understanding the biology of KRAS-G12D cancers, and identifying biomarkers that predict therapeutic response is crucial. In this Review, we discuss the genomics and biology of KRAS-G12D adenocarcinomas, including histological features, transcriptional landscape, the immune microenvironment, and how these factors influence response to therapy. Moreover, we explore potential therapeutic strategies using novel G12D inhibitors, leveraging knowledge gained from clinical trials using G12C inhibitors.