MDR1 Mutation in Dogs: Why It Matters During Chemotherapy
Updated: Oct 2
If you're planning chemotherapy for a dog, MDR1 status may not always be the first thing that comes to mind.
But in certain patients, particularly predisposed breeds, it can have an important influence on how safely some chemotherapy drugs are handled.
So, what exactly is MDR1? What does P-glycoprotein do? And why can an MDR1 mutation make some dogs more susceptible to chemotherapy toxicity?
Let's take a closer look.
What is MDR1 and P-glycoprotein?
P-glycoprotein is a naturally occurring protein that helps remove certain drugs from cells.
I tend to think of it as a protective transport pump. It helps the body move and eliminate certain drugs, including some of the medications we use in veterinary oncology.
P-glycoprotein is produced by the MDR1 gene, also known as ABCB1.
Most of the time, this process quietly happens in the background. The issue arises when a dog has inherited an MDR1 mutation.
What happens if a dog has an MDR1 mutation?
Some dogs inherit a mutation that means they produce little or no functional P-glycoprotein.
Without that normal protective mechanism, certain chemotherapy drugs can remain in the body for longer. As a result, these dogs can be at greater risk of treatment related toxicity.
This is why knowing a dog's MDR1 status can become clinically relevant when we're making chemotherapy decisions.
It's not simply an interesting genetic finding. It can influence how we approach treatment for that individual patient.
Which chemotherapy drugs are affected by MDR1?
Dogs with an MDR1 mutation can be more likely to experience side effects from drugs transported by P-glycoprotein.
In oncology, these include:
Vincristine
Vinblastine
Doxorubicin and other anti-tumour antibiotics
This becomes particularly relevant when one of these drugs forms part of the treatment protocol we're considering.
For example, studies referenced in the original OncoTails post have shown that dogs with two copies of the MDR1 mutation are more likely to develop neutropenia, thrombocytopenia and gastrointestinal effects when treated with vincristine.
Which dog breeds are predisposed to the MDR1 mutation?
There are several breeds in which MDR1 mutations are recognised as a particular consideration.
These include:
Collies
Shetland Sheepdogs
Australian Shepherds
White Shepherds
Longhaired Whippets
For dogs from at risk breeds, genetic testing is recommended before administering drugs transported by P-glycoprotein.
Why does MDR1 testing matter in veterinary oncology?
This is really where the genetics become clinically useful.
Knowing that a patient carries an MDR1 mutation gives us information that can help when we're considering chemotherapy and the potential risk of toxicity.
And, as with so much in oncology, the important thing is the individual patient in front of us.
Breed, MDR1 status, the chemotherapy drug being considered and the wider clinical picture all need to be taken into account when planning treatment.
The aim isn't simply to follow a protocol. It's to make informed treatment decisions that are appropriate for that particular dog.
Every patient is different
An MDR1 mutation doesn't mean that we stop thinking about chemotherapy altogether.
What it does mean is that we have additional information to consider when planning treatment.
Understanding a dog's MDR1 status can help guide safer chemotherapy decisions and reduce the risk of avoidable toxicity.
That's why genetic status can be such a useful part of the conversation when managing an oncology patient from an at risk breed.
Need support with chemotherapy planning?
If you're managing an oncology patient and would like specialist input on chemotherapy planning, drug selection or the wider management of the case, OncoTails can help.
OncoTails provides specialist veterinary oncology support to veterinary teams, helping practices navigate treatment decisions while keeping care close to home.
Have an oncology case you'd like to discuss?
Dr Sarah Mason FRCVS Veterinary Oncologist & Founder, OncoTails
Frequently asked questions about MDR1 in dogs
What is the MDR1 mutation in dogs? The MDR1 mutation affects the gene responsible for producing P-glycoprotein, a protein involved in transporting certain drugs out of cells. Some affected dogs produce little or no functional P-glycoprotein, which can increase their susceptibility to toxicity from certain medications.
Which chemotherapy drugs are affected by MDR1? The chemotherapy drugs highlighted by OncoTails include vincristine, vinblastine and doxorubicin and other anti-tumour antibiotics.
Which dog breeds are at risk of an MDR1 mutation? Predisposed breeds highlighted in the original post include Collies, Shetland Sheepdogs, Australian Shepherds, White Shepherds and Longhaired Whippets.
Should dogs be tested for MDR1 before chemotherapy? For at risk breeds, genetic testing is recommended before administering drugs transported by P-glycoprotein.
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