KRAS Mutation in Cancer
OncogeneKirsten Rat Sarcoma Viral Oncogene Homolog
KRAS encodes a GTPase that activates the RAS/MAPK signaling pathway, promoting cell growth and survival. KRAS mutations are common in lung, colorectal, and pancreatic cancers.
What Is KRAS?
KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog) encodes a small GTPase protein that acts as a molecular switch in the RAS/MAPK signaling pathway. When activated by growth factor receptors, KRAS triggers a cascade of signals promoting cell growth, proliferation, and survival. KRAS mutations lock the protein in its active "on" state, driving continuous cell proliferation independent of external growth signals.
KRAS Mutations in Cancer
KRAS is one of the most commonly mutated oncogenes, found in approximately 25% of all human cancers. It is particularly prevalent in pancreatic ductal adenocarcinoma (~90%), colorectal cancer (~40%), and non-small cell lung cancer (~30%). The most frequent mutations occur at codons 12 (G12D, G12V, G12C), 13 (G13D), and 61 (Q61H), each with distinct biochemical properties and clinical implications.
Therapeutic Landscape
For decades, KRAS was considered "undruggable" due to the protein's smooth surface lacking obvious drug-binding pockets. This changed with the development of KRAS G12C inhibitors (sotorasib, adagrasib), which covalently bind to the mutant cysteine. These represent a breakthrough in precision oncology, particularly for lung adenocarcinoma. Research into inhibitors for other KRAS mutations (G12D, G12V) is rapidly advancing.
Morphological Associations
KRAS-mutant tumors display characteristic morphological features visible on H&E slides: mucinous differentiation patterns in colorectal cancer, specific growth patterns in lung adenocarcinoma, and altered stromal reactions. HistoAtlas quantifies these morphological differences computationally across cancer types, linking KRAS status to tissue-level changes in cell composition, density, and spatial organization.
Frequently Asked Questions
What is a KRAS mutation?
A KRAS mutation is a DNA change in the KRAS gene that locks the KRAS protein in its active state, continuously signaling cells to grow and divide. KRAS mutations are found in about 25% of all cancers and are especially common in pancreatic, colorectal, and lung cancers.
Is KRAS mutation hereditary?
KRAS mutations in cancer are almost always somatic (acquired, not inherited). However, germline KRAS mutations can cause developmental disorders like Noonan syndrome, which carries a modestly increased cancer risk. Standard cancer-associated KRAS mutations (G12C, G12D, etc.) are not passed from parent to child.
Can KRAS mutations be treated?
Yes — KRAS G12C mutations can now be treated with targeted inhibitors (sotorasib, adagrasib), approved for lung cancer and under investigation in other tumor types. Inhibitors for other KRAS mutations (G12D) are in clinical trials. KRAS-mutant tumors are typically resistant to EGFR-targeted therapies.