MDR1 Gene Mutation and Chemotherapy

The MDR1 gene (also called ABCB1) encodes the drug efflux pump P-glycoprotein. P-glycoprotein transports a wide variety of substances including the chemotherapy agents vincristine, vinblastine, vinorelbine, doxorubicin, paclitaxel, docetaxel, daunorubicin, etoposide, imatinib, actinomycin-D and others.

In chemotherapy patients with MDR1 gene mutation, p-glycoprotein expression is reduced or absent leading to increased intracellular drug concentrations and haematological and gastrointestinal toxicity.

A number of breeds are predisposed to this mutation, particularly herding breeds such as Collies, Border Collies, Shetland Sheepdogs, Australian Shepherd Dogs, English Shepherd Dogs, German Shepherd Dogs, White Shepherd Dogs, Longhaired Whippets, McNabs and others including mixed breeds.

Dog breeds that are predisposed to MDR1 mutation should be tested for the mutation before administering any chemotherapy agents that are substrates of the P-glycoprotein pump. More information on testing can be found on the Washington State University website. For further information on testing for MDR1 mutation in the UK contact PTDS and in Australia contact Vet Path Laboratory Services.

If a patient is identified as heterozygous or homozygous for MDR1 mutation all drugs that are substrates of the P-glycoprotein pump require significant dose reductions.

To find out more speak to your local veterinary oncologist or submit a consultation.