Loading
G12D is the commonest KRAS mutation, especially in pancreatic cancer, and has no approved drug yet. In bowel cancer any KRAS or NRAS mutation is a reason not to give EGFR antibodies, which is where the approvals sit.
KRAS G12D (c.35G>A) drives about 40 percent of pancreatic and 12 percent of colorectal cancers; G12V and G13D follow. No G12D-selective drug is approved: zoldonrasib (RMC-9805) and the pan-RAS(ON) inhibitor daraxonrasib are in trials (RASolute 302, NCT06625320, is the phase 3 in pancreatic cancer). The approvals that turn on non-G12C KRAS status are negative ones: cetuximab and panitumumab are labelled for KRAS wild-type (and RAS wild-type) metastatic colorectal cancer, with the therascreen KRAS RGQ PCR Kit, cobas KRAS test, FoundationOne CDx and Tempus xT CDx listed as companion diagnostics for detecting the absence of codon 12 and 13 mutations.
In plain words · KRAS is the most commonly mutated cancer gene, called 'undruggable' for 40 years until 2021.
A KRAS G12D, G12V or G13D result does not yet open a targeted tablet outside a trial, and in bowel cancer it means the EGFR antibodies cetuximab and panitumumab should not be used. In pancreatic cancer, trials of RAS inhibitors are recruiting and are worth asking about. Only a KRAS G12C result qualifies for the approved KRAS drugs.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
Presence of a KRAS codon 12 or 13 (or exon 3 and 4) mutation other than G12C by PCR or sequencing; for EGFR antibodies the selecting result is the absence of KRAS and NRAS mutations in exons 2, 3 and 4.
“KRAS wild-type (absence of mutations in codons 12 and 13)”
FDA: List of FDA-Authorized Companion Diagnostic Devices| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| KRAS wild-type (negative selector) FDA companion diagnostic row for the therascreen KRAS RGQ PCR Kit with Erbitux, P110030 (06 July 2012). | Cetuximab | Colorectal cancer | FDA | label |
| KRAS and NRAS wild-type (negative selector) FDA companion diagnostic rows for FoundationOne CDx and xT CDx with Vectibix. | Panitumumab | Colorectal cancer | FDA | label |
Also defined by RASolute 302: daraxonrasib versus chemotherapy in previously treated metastatic pancreatic cancer (ClinicalTrials.gov NCT06625320).
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| therascreen KRAS RGQ PCR Kit | QIAGEN Manchester | Colorectal Cancer - Tissue | Cetuximab | P110030 (07/06/2012) |
| therascreen KRAS RGQ PCR Kit | QIAGEN Manchester | Colorectal Cancer - Tissue | Panitumumab | P110027 (05/23/2014) |
| FoundationOne CDx | Foundation Medicine | Colorectal Cancer - Tissue (KRAS and NRAS wild-type) | Panitumumab | P170019 (11/30/2017) |
Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.
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.
The driver count is a prognostic score in itself, and the allele matters: G12D is the pancreatic allele with the worst outlook and the one the new selective inhibitors chase.
KRAS wild-type status should trigger fusion testing, ideally by RNA sequencing, because NRG1 fusions can be targeted by HER-family inhibitors and now by zenocutuzumab.
It is the allele-level prognosis behind reading the KRAS variant rather than 'KRAS mutant', and it shows the older EUS assay over-called wild-type (33%).
It supplies the chemistry behind the allele spectrum of lung cancer: the G to T transversion that the tobacco signature generates is why KRAS G12C dominates in lung and G12D dominates in bowel and pancreatic cancer.
Extended RAS testing (KRAS and NRAS exons 2, 3 and 4) became the standard before any EGFR antibody, and about one in six patients who would previously have been treated is now spared a drug that would have made things worse.
It created the negative predictive biomarker in solid tumour oncology and, with the panitumumab analysis of the same year, restricted EGFR antibodies to RAS wild-type disease worldwide.
Shares therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF), KRAS G12C, RAS wild-type (extended KRAS and NRAS testing), Cetuximab and the tag biomarker.
Shares therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF), Colorectal cancer, Non-small-cell lung cancer and the tag biomarker.
Shares therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF) and the tag biomarker.
Shares therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF) and the tag biomarker.
Shares Pancreatic ductal adenocarcinoma, Colorectal cancer, Non-small-cell lung cancer and the tag biomarker.
Shares STK11 or KEAP1 loss in KRAS-mutant lung adenocarcinoma, Non-small-cell lung cancer and the tag biomarker.
Shares therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF), Non-small-cell lung cancer and the tag biomarker.
Shares Pancreatic ductal adenocarcinoma, Colorectal cancer, Non-small-cell lung cancer and the tag biomarker.