KRAS

Also known as K-Ras, KRAS proto-oncogene

Tumour types

colorectal cancer, non-small cell lung cancer, pancreatic cancer

KRAS encodes a small GTPase central to RAS/MAPK signaling; activating mutations are common oncogenic drivers across several solid tumor types.

G12C is the most therapeutically targeted KRAS variant to date; other common hotspots include G12D, G12V, and G13D.

Clinical significance

KRAS G12C-mutant NSCLC is eligible for KRAS G12C inhibitor therapy following progression on prior systemic treatment.
fda — FDA-approved product labeling for KRAS G12C inhibitors
RAS mutation status, including KRAS, is used to exclude anti-EGFR monoclonal antibody therapy in metastatic colorectal cancer, since RAS-mutant tumors do not derive benefit.
ema — EMA product information for anti-EGFR monoclonal antibodies

FDA-approved treatments

Krazati (adagrasib) — KRAS G12C-mutated locally advanced or metastatic NSCLC after at least one prior systemic therapy; in combination with cetuximab for KRAS G12C-mutated metastatic colorectal cancer after prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy [fda]
Lumakras (sotorasib) — KRAS G12C-mutated locally advanced or metastatic NSCLC after at least one prior systemic therapy [fda]

Prevalence

KRAS mutations occur in approximately 25% of NSCLC and up to 45% of colorectal cancers; KRAS G12C specifically accounts for approximately 13% of NSCLC and 3%-4% of colorectal cancer cases. [fda]

Tests / detection method

NGS

Therapeutic pipeline

KRAS G12D and pan-RAS/multi-RAS inhibitors (KRAS G12D, KRAS G12V) [fda]

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