Gene:
TNFRSF8
tumor necrosis factor receptor superfamily, member 8

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 brentuximab vedotin and TNFRSF8

This label is on the FDA Biomarker List
Informative PGx

Summary

Brentuximab vedotin (Adcetris) is an antibody-drug conjugate (ADC) directed at TNFRSF8 (CD30), and nonclinical data suggests its anti-cancer mechanism of action is by binding to CD30-expressing cells and then releasing a small molecule that disrupts microtubules.

Annotation

Brentuximab vedotin (Adcetris) is indicated in patients with Hodgkin lymphoma or systemic anaplastic large cell lymphoma after at least one treatment failure.

Excerpt from the brentuximab vedotin (Adcetris) drug label:

12.1 Mechanism of Action
Brentuximab vedotin is an ADC. The antibody is a chimeric IgG1 directed against CD30. The small molecule, MMAE, is a microtubule disrupting agent. MMAE is covalently attached to the antibody via a linker. Nonclinical data suggest that the anticancer activity of ADCETRIS is due to the binding of the ADC to CD30-expressing cells, followed by internalization of the ADC-CD30 complex, and the release of MMAE via proteolytic cleavage. Binding of MMAE to tubulin disrupts the microtubule network within the cell, subsequently inducing cell cycle arrest and apoptotic death of the cells.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the brentuximab (Adcentris) drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Genes and/or phenotypes found in this label

  • CYP3A4
    • Drug interactions section, Pharmacokinetics section, metabolism/PK
    • source: FDA Label
  • CYP3A5
    • Drug interactions section, Pharmacokinetics section, metabolism/PK
    • source: FDA Label
  • TNFRSF8
    • Indications & usage section, Description section, Clinical pharmacology section, Mechanism of action section, other
    • source: FDA Label

last updated 10/25/2013

European Medicines Agency (EMA) Label for brentuximab vedotin and TNFRSF8

Genetic testing required

Summary

The EMA European Public Assessment Report (EPAR) contains information regarding the indication of brentuximab vedotin in patients with CD30-expressing tumour cells due to the drug's mechanism of action.

Annotation

Excerpt from the brentuximab vedotin (Adcetris) EPAR:

ADCETRIS is indicated for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL).


Mechanism of action
Brentuximab vedotin is an antibody drug conjugate (ADC) that delivers an antineoplastic agent that results in apoptotic cell death selectively in CD30-expressing tumour cells. Nonclinical data suggest that the biological activity of brentuximab vedotin results from a multi-step process. Binding of the ADC to CD30 on the cell surface initiates internalisation of the ADC-CD30 complex, which then traffics to the lysosomal compartment. Within the cell, a single defined active species, MMAE, is released via proteolytic cleavage. Binding of MMAE to tubulin disrupts the microtubule network within the cell, induces cell cycle arrest and results in apoptotic death of the CD30-expressing tumour cell. Classical HL and sALCL express CD30 as an antigen on the surface of their malignant cells. This expression is independent of disease stage, line of therapy or transplant status. These features make CD30 a target for therapeutic intervention.

This information is highlighted in the following sections:
Qualitative and quantitative composition, Therapeutic indications, Pharmacodynamic properties, Package leaflet: Information for the patient.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the brentuximab vedotin EMA drug label.

*Disclaimer: The contents of this page have not been endorsed by the EMA and are the sole responsibility of PharmGKB.


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.

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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?

Overview

Alternate Names:  None
Alternate Symbols:  CD30 (previous symbol); KI-1
PharmGKB Accession Id: PA36616

Details

Cytogenetic Location: chr1 : p36.22 - p36.22
GP mRNA Boundary: chr1 : 12123434 - 12204264
GP Gene Boundary: chr1 : 12113434 - 12207264
Strand: plus
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.
No related genes are available

Curated Information ?

Evidence Drug
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
brentuximab vedotin
No related diseases are available

LinkOuts

Entrez Gene:
943
OMIM:
153243
UCSC Genome Browser:
NM_001243
RefSeq RNA:
NM_001243
NM_152942
RefSeq Protein:
NP_001234
NP_694421
RefSeq DNA:
AC_000044
AC_000133
NC_000001
NT_021937
NW_001838534
NW_923572
UniProtKB:
TNR8_HUMAN (P28908)
Ensembl:
ENSG00000120949
GenAtlas:
TNFRSF8
GeneCard:
TNFRSF8
MutDB:
TNFRSF8
ALFRED:
LO056062T
HuGE:
TNFRSF8
Comparative Toxicogenomics Database:
943
ModBase:
P28908
HumanCyc Gene:
HS04456
HGNC:
11923

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