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KRAS is the most commonly mutated cancer gene, called 'undruggable' for 40 years until 2021.
KRAS mutations drive ~90% of pancreatic, ~40% of colorectal, and ~30% of lung adenocarcinomas. Sotorasib and adagrasib (G12C) were first; G12D inhibitors (MRTX1133, zoldonrasib) and pan-RAS(ON) inhibitors (daraxonrasib, RMC-6236, in phase 3 in pancreatic cancer) are the next wave. Combination with EGFR antibodies is needed in colorectal cancer.
In plain words · KRAS is the most commonly mutated cancer gene, called 'undruggable' for 40 years until 2021.
Backbone ribbon from PDB 6UT0. RCSB PDB 6UT0. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
Backbone ribbon with the bound drug in ball-and-stick (pink carbons). The wireframe view adds the pocket residues within 5 Å as a thin cage.
KRAS is the most commonly mutated cancer gene, called 'undruggable' for 40 years until 2021.
Small GTPase switch; oncogenic mutations lock it in the GTP-bound ON state. Adaptive feedback and secondary mutations drive resistance.
24 products aim at KRAS: vaccines, small molecules and other agents. Drugs fit a pocket that exists only in one shape of the mutant protein and hold it there, off.
Phase 3 in first-line KRAS G12C-mutant NSCLC. Timing is a registry-based estimate. Source
The first phase 3 comparing KRAS G12C inhibitors head to head. Timing is a registry-based estimate. Source
Tumour-specific alteration: 2 of 2 label readouts filed under it measure a sequence variant (KRAS G12C, KRAS G12D (and other non-G12C KRAS mutations)) absent from normal cells. HPA KRAS: RNA low tissue specificity; high antibody staining in 7 normal tissues; highest cancer staining ovarian cancer (2 of 9 high). Distribution: 6 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Colorectal cancer, Lung cancer (all types), Pancreatic ductal adenocarcinoma, Biliary tract cancer (all types), Endometrial cancer, Ovarian cancer); Open Targets associates it with 24 specific cancer types at or above 0.5 (non-small cell lung carcinoma, gastric cancer, acute myeloid leukemia, linear nevus sebaceous syndrome, lung adenocarcinoma, urinary bladder cancer and more). (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: KRAS G12C label threshold; KRAS G12D (and other non-G12C KRAS mutations) label threshold; Human Protein Atlas KRAS tissue; Open Targets ENSG00000133703 associations
First described 1983. Earliest sequence paper UniProt cites for the protein: McGrath J.P. et al, Nature, 1983, "Structure and organization of the human Ki-ras proto-oncogene and a related processed pseudogene". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Cell lines and mouse models for this target →
Small GTPase switch; oncogenic mutations lock it in the GTP-bound ON state. Adaptive feedback and secondary mutations drive resistance.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Bone marrow, Cerebellum, Cerebral cortex, Endometrium, Epididymis, Fallopian tube, Kidney, Lymph node.
Medium only: carcinoid, endometrial cancer, head and neck cancer, liver cancer.
HPA KRAS tissue · HPA KRAS pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Pancreatic ductal adenocarcinoma | 88-94% | Activating mutation (any allele) | 88% of 3,594 targeted-panel samples (Singhi 2019); 2,217 of 2,483, 89.3%, in the Caris cohort (Philip 2022); more than 90% of 109 microdissected exomes (Witkiewicz 2015); cBioPortal: 2,188 of 2,336, 93.7%, in pdac_msk_2024; 361 of 395, 91.4%, in pancreas_msk_2024; 135 of 140, 96.4%, in paad_cptac_2021; 344 of 383, 89.8%, in paad_qcmg_uq_2016; 100 of 109, 91.7%, in paad_utsw_2015; 94 of 99, 94.9%, in paad_icgc. A subset of tumours carries multiple KRAS mutations, some biallelic (Cancer Genome Atlas 2017); mutant KRAS copy gains were recorded in 296 of 853 dosage-annotated pdac_msk_2024 samples (2 or more extra copies in 201, 3 or more in 95). | doi.org |
| Pancreatic ductal adenocarcinoma | 85-90% | Any KRAS mutation | G12D ~40%, G12V ~30%, G12R ~15%, G12C ~1-2% | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 49-59% | G12V, G12D, G12A, G13X and Q61X (share of KRAS mutation records) | cBioPortal, mutation records in luad_mskcc_2023_met_organotropism: G12V 119 of 797 (14.9%), G12D 97 (12.2%), G12A 72 (9.0%), G13C 32 (4.0%), Q61H 30 (3.8%), G13D 30 (3.8%), G12R 11, G12S 10, G12F 6, Q61L 6. In lung_msk_2017: G12D 37 of 244 (15.2%), G12V 37 (15.2%), G12A 19, G13D 12, Q61H 11. | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 41-51% | G12C allele (share of KRAS mutation records) | cBioPortal, mutation records: 344 of 797, 43.2%, in luad_mskcc_2023_met_organotropism; 268 of 526, 50.9%, in nsclc_ctdx_msk_2022; 104 of 244, 42.6%, in lung_msk_2017; 70 of 172, 40.7%, in luad_tcga_pan_can_atlas_2018; 96 of 224, 42.9%, in nsclc_tcga_broad_2016; 36 of 87, 41.4%, in nsclc_pd1_msk_2018. That is about 13% of all lung adenocarcinomas (344 of 2,653 samples in luad_mskcc_2023_met_organotropism). | cBioPortal (TCGA) |
| Colorectal cancer | 40-45% | Any KRAS mutation | G12C ~3-4% | cBioPortal (TCGA) |
| Colorectal cancer | 40-44% | Activating mutation (any allele) | cBioPortal: 3,096 of 7,237, 42.8%, in crc_msk_2026; 495 of 1,134, 43.7%, in crc_msk_2017; 666 of 1,516, 43.9%, in crc_eo_2020; 218 of 534, 40.8%, in coadread_tcga_pan_can_atlas_2018; 94 of 224, 42.0%, in coadread_tcga_pub; 173 of 619, 27.9%, in coadread_dfci_2016; 239 of 1,015, 23.5%, in crc_sysucc_2022. In CO.17, 42.3% of 394 evaluable tumours carried a K-ras exon 2 mutation (Karapetis 2008); ras-gene mutations were present in 58% of adenomas larger than 1 cm but only 9% of adenomas under 1 cm (Vogelstein 1988). | cBioPortal (TCGA) |
| Pancreatic ductal adenocarcinoma | 39-41% | G12D allele (share of KRAS mutation records) | 889 of 2,188 KRAS mutation records, 40.6%, in pdac_msk_2024 (the study's own KRAS_VARIANT attribute: 892 G12D, 706 G12V, 352 G12R, 111 Q61H, 37 Q61R, 26 G12C, 70 other); 136 of 344, 39.5%, in paad_qcmg_uq_2016; 61 of 135, 45.2%, in paad_cptac_2021; 39 of 95, 41.1%, in paad_icgc; 49 of 119, 41.2%, in paad_tcga_pan_can_atlas_2018; 37 of 100, 37.0%, in paad_utsw_2015 (cBioPortal). Among 219 advanced patients genotyped on EUS-guided biopsies, G12D 73, G12V 53, G12R 21 (Bournet 2016). | cBioPortal (TCGA) |
| Pancreatic ductal adenocarcinoma | 28-37% | G12V allele (share of KRAS mutation records) | 709 of 2,188, 32.4%, in pdac_msk_2024; 108 of 344, 31.4%, in paad_qcmg_uq_2016; 40 of 135, 29.6%, in paad_cptac_2021; 35 of 95, 36.8%, in paad_icgc; 33 of 119, 27.7%, in paad_tcga_pan_can_atlas_2018; 40 of 100, 40.0%, in paad_utsw_2015 (cBioPortal, mutation records). 53 of 147 codon-12 mutations in 219 advanced patients (Bournet 2016). | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 27-33% | Activating mutation (any allele) | cBioPortal: 787 of 2,653, 29.7%, in luad_mskcc_2023_met_organotropism; 241 of 915, 26.3%, in lung_msk_2017; 168 of 566, 29.7%, in luad_tcga_pan_can_atlas_2018; 75 of 230, 32.6%, in luad_tcga_pub; 33 of 110, 30.0%, in luad_cptac_2020; 33 of 302, 10.9%, in luad_oncosg_2020; 17 of 232, 7.3%, in lung_nci_2022. The Lung Cancer Mutation Consortium found KRAS in 182 of 733 fully genotyped adenocarcinomas, 25%, the commonest single driver in that series (Kris 2014). | cBioPortal (TCGA) |
| Colorectal cancer | 27-29% | G12D allele (share of KRAS mutation records) | cBioPortal, mutation records: 908 of 3,169, 28.7%, in crc_msk_2026; 137 of 504, 27.2%, in crc_msk_2017; 191 of 680, 28.1%, in crc_eo_2020; 58 of 223, 26.0%, in coadread_tcga_pan_can_atlas_2018; 45 of 177, 25.4%, in coadread_dfci_2016; 73 of 243, 30.0%, in crc_sysucc_2022. | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 25-30% | Adenocarcinoma, any KRAS mutation | G12C ~13% of adenocarcinoma | cBioPortal (TCGA) |
| Colorectal cancer | 16-24% | G13D allele (share of KRAS mutation records) | cBioPortal, mutation records: 569 of 3,169, 18.0%, in crc_msk_2026; 90 of 504, 17.9%, in crc_msk_2017; 118 of 680, 17.4%, in crc_eo_2020; 37 of 223, 16.6%, in coadread_tcga_pan_can_atlas_2018; 43 of 177, 24.3%, in coadread_dfci_2016; 55 of 243, 22.6%, in crc_sysucc_2022. | cBioPortal (TCGA) |
| Colorectal cancer | 16-22% | G12V allele (share of KRAS mutation records) | cBioPortal, mutation records: 622 of 3,169, 19.6%, in crc_msk_2026; 101 of 504, 20.0%, in crc_msk_2017; 140 of 680, 20.6%, in crc_eo_2020; 49 of 223, 22.0%, in coadread_tcga_pan_can_atlas_2018; 24 of 177, 13.6%, in coadread_dfci_2016; 38 of 243, 15.6%, in crc_sysucc_2022. | cBioPortal (TCGA) |
| Endometrial cancer | 15-20% | Any KRAS mutation | cBioPortal (TCGA) | |
| Colorectal cancer | 16-18% | Codon 59, 61, 117 or 146 mutation (share of KRAS missense records) | cBioPortal, missense records: 491 of 3,155, 15.6%, in crc_msk_2026 (codons 59 and 61, 152; codons 117 and 146, 270; other, 69); 85 of 503, 16.9%, in crc_msk_2017; 17 of 93, 18.3%, in coadread_tcga_pub; 104 of 676, 15.4%, in crc_eo_2020. A146T alone is 185 of 3,169 KRAS records in crc_msk_2026 and 33 of 504 in crc_msk_2017. | cBioPortal (TCGA) |
| Pancreatic ductal adenocarcinoma | 12-21% | G12R allele (share of KRAS mutation records) | 354 of 2,188, 16.2%, in pdac_msk_2024; 61 of 344, 17.7%, in paad_qcmg_uq_2016; 23 of 135, 17.0%, in paad_cptac_2021; 16 of 95, 16.8%, in paad_icgc; 25 of 119, 21.0%, in paad_tcga_pan_can_atlas_2018; 12 of 100, 12.0%, in paad_utsw_2015 (cBioPortal, mutation records). G12R is almost unique to pancreatic cancer among KRAS-driven tumours and carried the longest survival of the codon-12 alleles, 14 months, in 219 advanced patients (Bournet 2016). | cBioPortal (TCGA) |
| Ovarian cancer | 10-15% | Low-grade serous and mucinous | cBioPortal (TCGA) | |
| Gallbladder cancer | 11% | Mutation (amplification rarer) | 11% of 244 samples (Giraldo 2022; cBioPortal gbc_mskcc_2022: mutation in 18 of 244, 7.4%, and amplification in 10 of 244, 4.1%); 7.8% of 57 (Li 2014); 7% of 376 Indian patients (Suryavanshi 2025); 7.8% of 103 samples in cBioPortal gbc_msk_2018. | doi.org |
| Pancreatic ductal adenocarcinoma | 6-12% | No KRAS mutation (fusion and alternative-driver search) | 266 of 2,483, 10.7% (Philip 2022); 12% of 3,594 (Singhi 2019); 148 of 2,336, 6.3%, in pdac_msk_2024; 39 of 383, 10.2%, in paad_qcmg_uq_2016; 5 of 99 by the study's KRAS_MUTATION attribute in paad_icgc; 34 of 395, 8.6%, in pancreas_msk_2024 (cBioPortal). Among KRAS wild-type tumours: TP53 mutated in 44.5%, BRAF in 13.0%, fusions of BRAF 6.6%, FGFR2 5.2%, ALK 2.6%, RET 1.3% and NRG1 1.3%, amplification of FGF3 3%, ERBB2 2.2%, FGFR3 1.8%, NTRK 1.8% and MET 1.3%; MSI-high 4.7% against 0.7% and TMB-high 4.5% against 1% in KRAS-mutant disease (Philip 2022). KRAS wild-type TCGA tumours carried GNAS, BRAF, CTNNB1 and other RAS-pathway alterations (Cancer Genome Atlas 2017); all 4 of 17 young adults (Heining 2018) and all 3 of 47 patients (Jones 2019) with wild-type tumours carried a kinase or NRG1 fusion on whole-genome sequencing. | doi.org |
| Colorectal cancer | 6-9% | G12C allele (share of KRAS mutation records) | cBioPortal, mutation records: 219 of 3,169, 6.9%, in crc_msk_2026; 32 of 504, 6.3%, in crc_msk_2017; 42 of 680, 6.2%, in crc_eo_2020; 15 of 223, 6.7%, in coadread_tcga_pan_can_atlas_2018; 16 of 177, 9.0%, in coadread_dfci_2016; 13 of 243, 5.3%, in crc_sysucc_2022. That is about 3% of all colorectal cancers. Among 839 KRAS-mutant metastatic patients, 145, 17%, carried G12C, more often men and with lung and liver metastases, and their overall survival was shorter than with other KRAS alleles (hazard ratio 1.32) (Schirripa 2020). | cBioPortal (TCGA) |
| Pancreatic ductal adenocarcinoma | 5-8% | Q61H, Q61R, Q61L or Q61K allele (share of KRAS mutation records) | 167 of 2,188, 7.6% (Q61H 107, Q61R 38, Q61L 14, Q61K 8), in pdac_msk_2024; 23 of 344, 6.7% (Q61H 19), in paad_qcmg_uq_2016; 8 of 135, 5.9%, in paad_cptac_2021; 5 of 95, 5.3%, in paad_icgc; 8 of 119, 6.7%, in paad_tcga_pan_can_atlas_2018; 7 of 100, 7.0%, in paad_utsw_2015 (cBioPortal, mutation records). Codon 61 alleles were selectively associated with improved survival among 109 microdissected cancers (Witkiewicz 2015). | cBioPortal (TCGA) |
| Pancreatic ductal adenocarcinoma | 1-2% | G12C allele (share of KRAS mutation records) | About 1 to 2% of pancreatic cancers (Strickler 2023); 28 of 2,188 KRAS mutation records, 1.3%, and 26 of 2,194 samples with a KRAS_VARIANT call, 1.2%, in pdac_msk_2024; 6 of 344, 1.7%, in paad_qcmg_uq_2016; 4 of 100, 4.0%, in paad_utsw_2015; 3 of 361 in pancreas_msk_2024; 1 of 135 in paad_cptac_2021; 1 of 119 in paad_tcga_pan_can_atlas_2018 (cBioPortal). CodeBreaK 100 treated 38 previously treated patients: 8 centrally confirmed responses, 21%, progression-free survival 4.0 months, overall survival 6.9 months (Strickler 2023); KRYSTAL-1 gave 7 of 21 pancreatic responses, 33.3%, to adagrasib (Bekaii-Saab 2023). | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Adagrasib was the second KRAS G12C inhibitor, with a long half-life and brain penetration, and is approved in lung and colorectal cancer.
Avutometinib plus defactinib is the first treatment approved specifically for low-grade serous ovarian cancer, a slow-growing type driven by the RAS pathway.
Calderasib is an experimental small-molecule drug from Merck Sharp & Dohme in phase 3 trials for non-small-cell lung cancer and colorectal cancer, aimed at KRAS.
The first drug that blocks all active RAS variants, approved by the FDA in August 2026 for metastatic pancreatic cancer, where KRAS drives 90% of tumours.
Divarasib is Roche's KRAS G12C pill, the first to beat the two approved KRAS drugs head-to-head (July 2026).
A ready-made vaccine against the seven commonest KRAS mutations, given after pancreatic cancer surgery. Its phase 2 missed the main goal in 2026 but showed signs of activity.
A next-generation KRAS G12C drug that hits the active form of the protein, from the same company as daraxonrasib.
Fulzerasib was the first KRAS G12C-blocking pill approved in China, for lung cancers carrying that mutation after earlier treatment.
Garsorasib is InventisBio's KRAS G12C-blocking pill, approved in China in 2024 for previously treated lung cancer with that mutation.
GFH375 is an experimental small-molecule drug from Genfleet Therapeutics (Shanghai) in phase 3 trials for pancreatic ductal adenocarcinoma and non-small-cell lung cancer, aimed at KRAS.
Glecirasib is Jacobio's KRAS G12C inhibitor, approved in China in 2024 for previously treated non-small cell lung cancer with that mutation, and in a phase 3 trial against docetaxel.
A blood test that reads a tumour's mutations without a tissue biopsy and is the FDA-approved gateway to several targeted drugs.
INCB161734 is an experimental small-molecule drug from Incyte in phase 3 trials for pancreatic ductal adenocarcinoma, aimed at KRAS.
JDQ443 is an experimental small-molecule drug from Novartis Pharmaceuticals in phase 3 trials for non-small-cell lung cancer and colorectal cancer, aimed at KRAS.
JYP0015 is an experimental small-molecule drug from Guangzhou JOYO Pharma in phase 2 trials for pancreatic ductal adenocarcinoma, non-small-cell lung cancer and colorectal cancer, aimed at KRAS.
MRTX1133 was the first potent chemical tool against KRAS G12D, and proved the mutation could be drugged even though it lacks the reactive handle G12C has.
Olomorasib is Lilly's KRAS G12C pill, designed to combine safely with immunotherapy in first-line lung cancer.
A blood test approved with adagrasib to find the KRAS G12C mutation in lung cancer when a tissue biopsy is not possible.
Setidegrasib is an experimental investigational agent whose form is not stated in the registry from Astellas Pharma Global Development in phase 3 trials for pancreatic ductal adenocarcinoma and non-small-cell lung cancer, aimed at KRAS.
Sotorasib (Lumakras) was the first drug to hit KRAS, approved in 2021 after four decades of failure.
Tempus's tumour-and-normal gene panel, FDA-approved in 2023 as a companion test for EGFR antibodies in bowel cancer.
A family of quick single-gene tests that decide who can have several bowel, lung, breast and bladder cancer drugs.
VS-7375 is an experimental small-molecule drug from Verastem in phase 2 trials for pancreatic ductal adenocarcinoma, non-small-cell lung cancer and colorectal cancer, aimed at KRAS.
The first drug aimed specifically at KRAS G12D, the single most common mutation in pancreatic cancer. Early combination data in 2026 showed half of previously treated patients responding.
The 48 most recent of 92 papers; see them all →
One of the most cited trial reports Europe PMC returns for Daraxonrasib in Pancreatic ductal adenocarcinoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
Useful for a patient offered adagrasib after chemotherapy or immunotherapy who wants the trial explained without jargon. It adds no new data; the primary KRYSTAL-12 publication and the trial page remain the reference for the numbers.
For gallbladder cancer the points that matter are that HER2 can disappear under HER2-directed pressure, that SMAD4 co-mutation predicts a worse response, and that sequencing at progression, not just at diagnosis, may be needed to guide the next line.
HER2 is as frequent in India as in the West, so HER2 testing pays off in the highest-incidence population, while tumour-agnostic immunotherapy markers will rarely apply. The paper also shows plasma testing is feasible where tissue is scarce.
Evidence that the immune environment of gallbladder cancer differs by population even when the mutations do not; a reason to report gallbladder cancer and its regions separately in immunotherapy trials rather than as one biliary subgroup.
The mechanism that let one drug address G12D, G12V and G12R together, which is why the RASolute 302 trial could enrol unselected pancreatic cancer and nearly double survival.
It is the positive half of the tumour mutational burden story and it applies only to single-agent immunotherapy, which is the setting fewest patients are treated in.
This is the result that ended tumour mutational burden as a practical selector in lung cancer: in the regimen most patients receive, it selects nobody, and neither do the co-mutations most often quoted as reasons to withhold immunotherapy.
Query for this target: (TITLE:"KRAS" OR ABSTRACT:"KRAS") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about KRAS, not a curated reading list.
Shares Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway, Ryan B. Corcoran, Downstream and upstream, NCIC CO.17 and the tag driver.
Shares Ryan B. Corcoran, Downstream and upstream, Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia, Elena Élez and the tag driver.
Shares Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway, Imagene AI, Cogent Biosciences, Molecular and clinical determinants of targeted therapy treatment in biliary tract cancer and the tag driver.
Shares BridgeBio Oncology Therapeutics, Cogent Biosciences, Classifying colorectal cancer by tumor location rather than sidedness highlights a continuum in mutation profiles and consensus molecular subtypes, Oncogene and the tag driver.
Shares LUNGevity Foundation (and GO2 for Lung Cancer), Imagene AI, Inivata, Lucence and the tag driver.
Shares Imagene AI, Lucence, NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer, nationales Netzwerk Genomische Medizin Lungenkrebs and the tag driver.
Shares Lucence, Molecular and clinical determinants of targeted therapy treatment in biliary tract cancer, Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention, Thyroid cancer (KEGG map) and the tag driver.
Shares Cogent Biosciences, Biliary cancer: utility of next-generation sequencing for clinical management, Tanios Bekaii-Saab, Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention and the tag driver.