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Next batter up! Targeting cancers with KRAS-G12D mutations
Mara N Zeissig1, Lauren M Ashwood2, Olga Kondrashova2
1ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, 3052, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, 3052, Australia.
Trends in Cancer
|August 17, 2023
Summary
KRAS G12D mutations drive many cancers. This review explores KRAS-G12D cancer biology, biomarkers, and new G12D inhibitor therapies, drawing insights from KRAS-G12C inhibitor trials.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- KRAS is the most frequently mutated oncogene in cancer.
- KRAS G12D mutations are highly prevalent in carcinomas and adenocarcinomas.
- Targeted therapies for KRAS mutations are advancing rapidly.
Purpose of the Study:
- To review the genomics and biology of KRAS-G12D driven cancers.
- To identify biomarkers predicting therapeutic response to KRAS-G12D inhibitors.
- To explore novel therapeutic strategies for KRAS-G12D cancers.
Main Methods:
- Review of existing literature on KRAS-G12D.
- Analysis of genomic and transcriptomic data.
- Examination of the tumor immune microenvironment.
- Evaluation of clinical trial data for KRAS inhibitors.
Main Results:
- KRAS-G12D cancers exhibit specific histological and transcriptional features.
- The immune microenvironment plays a role in therapeutic response.
- Biomarkers for predicting response are being identified.
- Novel G12D inhibitors show promise.
Conclusions:
- Understanding KRAS-G12D biology is critical for effective treatment.
- Biomarker identification is key to personalized therapy.
- New G12D inhibitors offer potential therapeutic avenues.
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