{"entity":{"id":"ras-wild-type","kind":"biomarker","name":"RAS wild-type (extended KRAS and NRAS testing)","aka":["RAS wild-type","RAS wild type","KRAS wild-type","KRAS wild type","wild-type RAS","extended RAS","extended RAS testing","RAS/BRAF wild-type","pan-RAS wild-type","RAS-WT"],"tldr":"RAS wild-type is the absence of a mutation, and it is the result that decides whether the EGFR antibodies cetuximab and panitumumab can be given in bowel cancer. Extended testing means KRAS and NRAS exons 2, 3 and 4, not just codons 12 and 13.","summary":"This is a negative selector: the drug is given when nothing is found. Cetuximab and panitumumab only work in metastatic colorectal cancer whose RAS genes are unmutated, because a mutation downstream of the receptor makes blocking the receptor pointless. The definition widened once. The 2012 and 2014 companion diagnostic claims asked only for KRAS codons 12 and 13 (exon 2); the PRIME extended analysis (Douillard, New England Journal of Medicine 2013) then showed that patients with RAS mutations outside exon 2, in KRAS or NRAS exons 3 and 4, did worse when panitumumab was added, so the wild-type definition was extended to KRAS and NRAS exons 2, 3 and 4 and the panitumumab label and its companion diagnostics were rewritten around it. The FDA list now carries both definitions side by side: FoundationOne CDx, xT CDx, the CRCDx RAS Mutation Detection Assay and MI Cancer Seek report KRAS and NRAS wild-type across exons 2, 3 and 4 for panitumumab, while the cetuximab rows on the same devices, on the therascreen KRAS RGQ PCR Kit and on ONCO/Reveal Dx still read codons 12 and 13. An assay that reads codons 12 and 13 alone misses about one KRAS mutation in six and nearly every NRAS mutation, so a codon 12 and 13 wild-type result is not the same claim as an extended RAS wild-type result. Sidedness is read alongside it: in RAS wild-type disease an EGFR antibody improves survival in left-sided tumours and not in right-sided ones. RAS wild-type is also the setting for the HER2-directed colorectal combinations and, with a BRAF V600E mutation, for encorafenib with cetuximab.","asOf":"2026-09-23","links":[{"label":"FDA: List of FDA-Authorized Companion Diagnostic Devices","url":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"label":"Douillard et al., PRIME extended RAS analysis (NEJM 2013)","url":"https://doi.org/10.1056/NEJMoa1305275"}],"tags":["biomarker","kras","negative-selector"],"related":["kras-g12d","kras-g12c","braf-v600e"],"cancers":["colorectal","rectal-cancer","colon-cancer","her2-amplified-colorectal","braf-v600e-colorectal"],"sections":[],"technologies":["companion-diagnostic"],"targets":[],"drugs":["cetuximab","panitumumab","encorafenib","tucatinib","trastuzumab","sotorasib","adagrasib","therascreen-cdx","tempus-xt-cdx","foundationone-cdx","caris-mi-cancer-seek"],"companies":[],"institutions":[],"pathways":[],"terms":["wild-type","extended-ras-testing","sidedness","ngs"],"trials":["prime","paradigm","crystal-fire3","calgb-80405","opus","codebreak-300","mountaineer"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"kras","measurement":"sequencing-variant","scoringRule":{"text":"No activating mutation detected in KRAS or NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61) or exon 4 (codons 117 and 146) by PCR or sequencing of tumour tissue. Older cetuximab claims test KRAS codons 12 and 13 only; the label wording differs between the two antibodies and the report should say which was done.","quote":"KRAS wild-type (absence of mutations in exons 2, 3, and 4) and NRAS wild type (absence of mutations in exons 2, 3, and 4)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools","sourceLabel":"FDA: List of FDA-Authorized Companion Diagnostic Devices"},"thresholds":[{"value":"KRAS and NRAS wild-type across exons 2, 3 and 4","drugId":"panitumumab","cancerId":"colorectal","regulator":"FDA","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools","quote":"KRAS wild-type (absence of mutations in exons 2, 3, and 4) and NRAS wild type (absence of mutations in exons 2, 3, and 4)","status":"current","note":"FDA companion diagnostic row for FoundationOne CDx with Vectibix, P170019 (30 November 2017); xT CDx (P210011), the CRCDx RAS Mutation Detection Assay Kit (P220005) and MI Cancer Seek (P240010) carry the same wording."},{"value":"KRAS wild-type at codons 12 and 13","drugId":"cetuximab","cancerId":"colorectal","regulator":"FDA","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools","quote":"KRAS wild-type (absence of mutations in codons 12 and 13)","status":"current","note":"FDA companion diagnostic row for FoundationOne CDx with Erbitux, P170019 (30 November 2017); the therascreen KRAS RGQ PCR Kit (P110027/S013, 2 December 2022), ONCO/Reveal Dx (P200011) and xT CDx (P210011) carry the same exon 2 wording. Guidelines ask for extended RAS testing before either antibody."}],"definedBy":{"label":"Douillard et al., New England Journal of Medicine 2013: panitumumab with FOLFOX4 in the PRIME trial, the extended RAS analysis that widened the wild-type definition to KRAS and NRAS exons 2, 3 and 4","url":"https://doi.org/10.1056/NEJMoa1305275"},"tests":["foundationone-cdx","tempus-xt","caris-mi-cancer-seek","guardant360-cdx"],"assays":["kras-therascreen","foundationone-cdx-panel"],"companionDiagnostics":[{"device":"FoundationOne CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["panitumumab"],"indication":"Colorectal Cancer - Tissue (KRAS and NRAS wild-type, exons 2, 3 and 4)","pma":"P170019 (11/30/2017)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"FoundationOne CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["cetuximab"],"indication":"Colorectal Cancer - Tissue (KRAS wild-type, codons 12 and 13)","pma":"P170019 (11/30/2017)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"xT CDx","maker":"Tempus Labs","companyId":"tempus","drugs":["panitumumab"],"indication":"Colorectal Cancer (CRC) - Tissue (matching blood or saliva), KRAS and NRAS wild-type","pma":"P210011 (04/28/2023)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"xT CDx","maker":"Tempus Labs","companyId":"tempus","drugs":["cetuximab"],"indication":"Colorectal Cancer (CRC) - Tissue (matching blood or saliva), KRAS wild-type at codons 12 or 13","pma":"P210011 (04/28/2023)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"CRCDx RAS Mutation Detection Assay Kit","maker":"EntroGen","drugs":["panitumumab"],"indication":"Colorectal Cancer (CRC) - Tissue","pma":"P220005 (09/29/2023)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"MI Cancer Seek (MCS)","maker":"Caris Life Sciences","companyId":"caris","drugs":["panitumumab"],"indication":"Colorectal Cancer - Tissue","pma":"P240010 (11/05/2024)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"therascreen KRAS RGQ PCR Kit","maker":"QIAGEN Manchester","companyId":"qiagen","drugs":["cetuximab"],"indication":"Colorectal Cancer - Tissue (KRAS wild-type, codons 12 and 13)","pma":"P110027/S013 (12/02/2022)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"ONCO/Reveal Dx Lung and Colon Cancer Assay","maker":"Pillar Biosciences","drugs":["cetuximab","panitumumab"],"indication":"Colorectal Cancer - Tissue","pma":"P200011 (07/30/2021)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"RAS wild-type is good news in metastatic bowel cancer: it means the EGFR antibodies cetuximab and panitumumab are options, usually alongside chemotherapy. Ask whether the test was extended RAS, covering KRAS and NRAS exons 2, 3 and 4, because the older tests looked only at two spots in KRAS and can call a tumour wild-type when it is not. Which side of the bowel the tumour started on is read alongside the result, because the antibodies work better in left-sided tumours. RAS wild-type is also needed for the HER2-directed combinations and for encorafenib with cetuximab when BRAF V600E is present."},"route":"/biomarkers/ras-wild-type/","neighbours":{"biomarker":[{"id":"braf-v600e","kind":"biomarker","name":"BRAF V600E (and V600K)","route":"/biomarkers/braf-v600e/"},{"id":"kras-g12c","kind":"biomarker","name":"KRAS G12C","route":"/biomarkers/kras-g12c/"},{"id":"kras-g12d","kind":"biomarker","name":"KRAS G12D (and other non-G12C KRAS mutations)","route":"/biomarkers/kras-g12d/"}],"cancer":[{"id":"braf-v600e-colorectal","kind":"cancer","name":"BRAF V600E-mutant colorectal cancer","route":"/cancers/braf-v600e-colorectal/"},{"id":"colon-cancer","kind":"cancer","name":"Colon cancer (adenocarcinoma of the colon)","route":"/cancers/colon-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"her2-amplified-colorectal","kind":"cancer","name":"HER2-amplified colorectal cancer","route":"/cancers/her2-amplified-colorectal/"},{"id":"rectal-cancer","kind":"cancer","name":"Rectal cancer","route":"/cancers/rectal-cancer/"}],"technology":[{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","route":"/technologies/companion-diagnostic/"}],"drug":[{"id":"adagrasib","kind":"drug","name":"Adagrasib","route":"/drugs/adagrasib/"},{"id":"cetuximab","kind":"drug","name":"Cetuximab","route":"/drugs/cetuximab/"},{"id":"encorafenib","kind":"drug","name":"Encorafenib","route":"/drugs/encorafenib/"},{"id":"foundationone-cdx","kind":"drug","name":"FoundationOne CDx / Liquid CDx","route":"/drugs/foundationone-cdx/"},{"id":"caris-mi-cancer-seek","kind":"drug","name":"MI Cancer Seek","route":"/drugs/caris-mi-cancer-seek/"},{"id":"panitumumab","kind":"drug","name":"Panitumumab","route":"/drugs/panitumumab/"},{"id":"sotorasib","kind":"drug","name":"Sotorasib","route":"/drugs/sotorasib/"},{"id":"tempus-xt-cdx","kind":"drug","name":"Tempus xT CDx","route":"/drugs/tempus-xt-cdx/"},{"id":"therascreen-cdx","kind":"drug","name":"therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF)","route":"/drugs/therascreen-cdx/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"tucatinib","kind":"drug","name":"Tucatinib","route":"/drugs/tucatinib/"}],"term":[{"id":"extended-ras-testing","kind":"term","name":"Extended RAS testing","route":"/terms/extended-ras-testing/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"id":"sidedness","kind":"term","name":"Sidedness (left vs right colon)","route":"/terms/sidedness/"},{"id":"wild-type","kind":"term","name":"Wild-type (WT)","route":"/terms/wild-type/"}],"trial":[{"id":"calgb-80405","kind":"trial","name":"CALGB/SWOG 80405","route":"/trials/calgb-80405/"},{"id":"codebreak-300","kind":"trial","name":"CodeBreaK 300","route":"/trials/codebreak-300/"},{"id":"crystal-fire3","kind":"trial","name":"CRYSTAL & FIRE-3","route":"/trials/crystal-fire3/"},{"id":"mountaineer","kind":"trial","name":"MOUNTAINEER","route":"/trials/mountaineer/"},{"id":"opus","kind":"trial","name":"OPUS","route":"/trials/opus/"},{"id":"paradigm","kind":"trial","name":"PARADIGM","route":"/trials/paradigm/"},{"id":"prime","kind":"trial","name":"PRIME","route":"/trials/prime/"}],"target":[{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"}],"paper":[{"id":"paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017","kind":"paper","name":"Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials","route":"/key-papers/paper-arnold-primary-tumour-side-ras-wild-type-ann-oncol-2017/"}]}}