Gene:
KRAS
v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.


last updated 10/25/2013

FDA Label for cetuximab and EGFR, KRAS

This label is on the FDA Biomarker List
Genetic testing required

Summary

Cetuximab is used in alone or in combination therapy to treat advanced squamous cell carcinoma of the head and neck and to treat K-Ras mutation-negative, EGFR expressing metastatic colorectal cancer. In cases of colorectal cancer, the label states "Determine K-Ras mutation and EGFR-expression status using FDA-approved tests prior to initiating treatment."

There's more of this label. Read more.


last updated 10/25/2013

FDA Label for panitumumab and EGFR, KRAS

This label is on the FDA Biomarker List
Genetic testing required

Summary

The panitumumab drug label contains information about EGFR-expressing metastatic colorectal carcinoma with disease progression on or following certain chemotherapy regimens. Detection of EGFR protein expression is necessary for selection of patients appropriate for Vectibix therapy. The label was updated to include information about treatment of patients with KRAS mutations. Retrospective subset analyses of metastatic colorectal cancer trials have not shown a treatment benefit for Vectibix in patients whose tumors had KRAS mutations in codon 12 or 13. Use of Vectibix is not recommended for the treatment of colorectal cancer with these mutations.

There's more of this label. Read more.


last updated 01/14/2014

FDA Label for regorafenib and EGFR, KRAS, VEGFA

Informative PGx

Summary

The FDA-approved drug label for regorafenib (Stivarga) states that it is intended for patients with metastatic colorectal cancer who were previously given fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if they were KRAS wild type, an anti-EGFR therapy. The label does not specifically mention any form of genetic testing. This drug-biomarker pair was previously in the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" but has subsequently been removed.

There's more of this label. Read more.



European Medicines Agency (EMA) Label for panitumumab and KRAS

Genetic testing required

Summary

The EMA European Public Assessment Report (EPAR) for panitumumab (Vectibix) contains information regarding the requirement for testing of KRAS mutations before initiating treatment, as the drug is indicated for patients with wildtype KRAS.

There's more of this label. Read more.


PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Related Drugs?
therascreen KRAS RGQ PCR Kit KRAS:Gly12Asp , KRAS:Gly12Ala , KRAS:Gly12Val , KRAS:Gly12Ser , KRAS:Gly12Arg , KRAS:Gly12Cys , KRAS:Gly13Asp
KRAS Mutation Detection Kit - Mutector II KRAS:Gly12Asp , KRAS:Gly12Ala , KRAS:Gly12Val , KRAS:Gly12Ser , KRAS:Gly12Arg , KRAS:Gly12Cys , KRAS:Gly13Asp , KRAS:Gly13Ser , KRAS:Gly13Arg , KRAS:Gly13Cys , KRAS:Gly13Ala , KRAS:Gly13Val

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA
rs61764370 *2505T>G, *2626T>G, 18120348A>C, 25360224A>C, 48631T>G
A > C
3' UTR
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  None
Alternate Symbols:  KRAS1
PharmGKB Accession Id: PA30196

Details

Cytogenetic Location: chr12 : p12.1 - p12.1
GP mRNA Boundary: chr12 : 25358180 - 25403854
GP Gene Boundary: chr12 : 25355180 - 25413854
Strand: minus
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Bisphosphonate Pathway, Pharmacodynamics
    Representation of genes involved in bisphosphonates' effects in osteoclasts.
  1. EGFR Inhibitor Pathway, Pharmacodynamics
    Model non-tissue specific cancer cell displaying genes that may be involved in the treatment using epidermal growth factor receptor specific tyrosine kinase inhibitors or monoclonal antibodies.
  1. Sorafenib Pharmacodynamics
    Mechanism of action of sorafenib
  1. VEGF Signaling Pathway
    Model endothelial cell displaying genes of the VEGF signalling pathway and the sites at which bevacizumab, sorafenib, sunitinib, brivanib and cilengitide are known to act.

External Pathways

Links to non-PharmGKB pathways.

  1. telomeres telomerase cellular aging and immortality - (BioCarta via Pathway Interaction Database)

Curated Information ?

Curated Information ?

Curated Information ?

Publications related to KRAS: 26

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Prioritizing genomic applications for action by level of evidence: a horizon-scanning method. Clinical pharmacology and therapeutics. 2014. Dotson W D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
The LCS6 polymorphism in the binding site of let-7 microRNA to the KRAS 3'-untranslated region: its role in the efficacy of anti-EGFR-based therapy in metastatic colorectal cancer patients. Pharmacogenetics and genomics. 2013. Sebio Ana, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy. Pharmacogenomics. 2013. Weng Liming, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A Novel Fully Automated Molecular Diagnostic System (AMDS) for Colorectal Cancer Mutation Detection. PloS one. 2013. Kitano Shiro, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics and pharmacogenomics: role of mutational analysis in anti-cancer targeted therapy. The pharmacogenomics journal. 2012. Savonarola A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Prospective-retrospective biomarker analysis for regulatory consideration: white paper from the industry pharmacogenomics working group. Pharmacogenomics. 2011. Patterson Scott D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Key pathways are frequently mutated in high risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011. Zhang Jinghui, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The Role of KRAS rs61764370 in Invasive Epithelial Ovarian Cancer: Implications for Clinical Testing. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. Pharoah Paul D P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB Conference on Pharmacogenetics and Pharmacogenomics. Pharmacogenomics. 2011. Becquemont Laurent, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetic tests in cancer chemotherapy: what physicians should know for clinical application. The Journal of pathology. 2011. Lee Soo-Youn, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomic contribution to drug response. Cancer journal (Sudbury, Mass.). 2011. Watson Roshawn G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic modulation of the Let-7 microRNA binding to KRAS 3'-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab-irinotecan. The pharmacogenomics journal. 2010. Graziano F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Targeted cancer therapies in the twenty-first century: lessons from imatinib. Clinical pharmacology and therapeutics. 2010. Stegmeier F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature. 2009. Barbie David A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics and biomarkers in colorectal cancer. The pharmacogenomics journal. 2009. Strimpakos A S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
K-ras mutations and benefit from cetuximab in advanced colorectal cancer. The New England journal of medicine. 2008. Karapetis Christos S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science (New York, N.Y.). 2008. Jones Sin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The cancer biomarker problem. Nature. 2008. Sawyers Charles L. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Network analysis of oncogenic Ras activation in cancer. Science (New York, N.Y.). 2007. Stites Edward C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nature genetics. 2007. Pandit Bhaswati, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nature genetics. 2007. Razzaque M Abdur, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. British journal of cancer. 2007. Di Fiore F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The consensus coding sequences of human breast and colorectal cancers. Science (New York, N.Y.). 2006. Sjöblom Tobias, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Germline missense mutations affecting KRAS Isoform B are associated with a severe Noonan syndrome phenotype. American journal of human genetics. 2006. Carta Claudio, et al. PubMed

LinkOuts

UniProtKB:
RASK_HUMAN (P01116)
Ensembl:
ENSG00000133703
GenAtlas:
KRAS
GeneCard:
KRAS
MutDB:
KRAS
ALFRED:
LO000285P
HuGE:
KRAS
Comparative Toxicogenomics Database:
3845
ModBase:
P01116
HumanCyc Gene:
HS05779
HGNC:
6407

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