Next batter up! Targeting cancers with KRAS-G12D mutations

作者：Mara N. Zeissig, Lauren M. Ashwood, Olga Kondrashova, Kate D. Sutherland · 发表于：Trends in cancer · 年份：2023 · DOI：10.1016/j.trecan.2023.07.010 · 被引用次数：126 · 研究领域：Colorectal Cancer Treatments and Studies、Cancer Immunotherapy and Biomarkers、Cancer Genomics and Diagnostics

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.