Target intelligence / Profile preview

Kirsten rat sarcoma viral oncogene homolog G12D (KRAS G12D)

Target: KRAS G12D
Molecular classification: GTPase, Oncoprotein

Overview

KRAS G12D is a point mutation in the KRAS gene, where glycine at position 12 is replaced by aspartic acid. This mutation leads to constitutive activation of the KRAS protein, driving oncogenic signaling and tumorigenesis in several cancer types, including pancreatic ductal adenocarcinoma, non-small cell lung cancer, and colorectal cancer. It is associated with poorer prognosis and resistance to certain therapies.

Other names: KRAS Gly12AspKRAS G12D mutationKRAS c.35G>AKRAS p.Gly12Asp

Mechanism of action

Constitutive activation of the RAS/MAPK pathway

Biological functions

Signal transductionCell proliferationCell survivalRAS/MAPK pathway activation

Disease associations

CancerPancreatic ductal adenocarcinomaNon-small cell lung cancerColorectal cancer

Safety considerations

Resistance to EGFR inhibitorsShorter overall survival in PDACTherapeutic challenges due to high-affinity nucleotide binding and minimal structural differences between wild-type/mutant proteins

Interacting drugs

Cetuximab

11 more in the full profile.

Biomarkers

KRAS G12D mutation for prognosis in PDACResistance to EGFR-targeted therapies in colorectal cancerKRAS G12D for response/resistance to targeted agents

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