What is the difference between KRAS G12D and KRAS G12C

According to the National Cancer Institute (NCI), KRAS mutations occur when there are changes in the KRAS gene, which produces proteins involved in cell signaling. The specific location of these mutations (G12D vs G12C) affects both prognosis and treatment options.

Key differences:

1. Molecular Structure: According to ASCO guidelines, KRAS G12C involves a substitution of glycine with cysteine at position 12, while KRAS G12D involves a substitution of glycine with aspartic acid at the same position. This molecular difference is crucial because it affects how drugs can target these mutations.

2. Treatment Options: The FDA has approved specific treatments for KRAS G12C mutations, including:

• Sotorasib (Lumakras) - approved in 2021 for KRAS G12C-mutated non-small cell lung cancer
• Adagrasib (Krazati) - also approved for KRAS G12C-mutated NSCLC

According to NCCN Guidelines, while KRAS G12C has targeted therapy options, KRAS G12D currently does not have FDA-approved targeted treatments. Patients with G12D mutations typically receive standard therapy options for their cancer type.

1. Frequency: The NCI notes that G12D mutations are more commonly found in pancreatic cancer, while G12C mutations are more frequently observed in lung cancer.

Always consult with your oncologist about your specific mutation and treatment options, as research in this field is rapidly evolving.