You don’t have to smoke to get lung cancer. Witness the nearly 40,000 dogs in the US who develop canine pulmonary adenocarcinoma (CPAC) each year.

CPAC is an aggressive disease that clinically resembles human lung cancer among people who’ve never smoked (also called never-smokers). There is no standard-of-care treatment for CPAC and little is known of the disease’s genetic underpinnings.

That could change dramatically, thanks to a groundbreaking new study by the Translational Genomics Research Institute (TGen) and The Ohio State University College of Veterinary Medicine that sheds new light on what causes CPAC—and may lead to a cure.

The researchers discovered that the same gene mutation that causes a particular kind of breast cancer in women—HER2—also appears to be the cause of CPAC in many dogs: nearly half the dogs in the study who had CPAC also had the HER2 mutation.

That lead the researchers to theorize that HER2-positive dogs with CPAC might respond to treatment with a drug called neratinib, which doctors have used successfully to treat human breast cancer. Neratinib inhibits the mutant, cancer-causing form of HER2 in people.

Based on the results from this study, a clinical trial using neratinib is planned for dogs with naturally occurring lung cancer who have the HER2 mutation.

NEWStat reached out to the study’s lead author, Gwendolen (Wendy) Lorch, DVM, PhD, DACVD, to find out more about the study and the upcoming clinical trial. Lorch is an associate professor in the Department of Veterinary Clinical Sciences at The Ohio State University College of Veterinary Medicine and will run the study’s clinical trial.

NEWStat: What makes this study so groundbreaking?

Wendy Lorch: This is the first comprehensive genomic profiling of canine lung cancer.

NEWStat: What are the implications for the treatment of CPAC?

WL: Using the genomic information, we were able to identify an activating mutation in an oncogene, HER2, [and treat it with neratinib,] which is a therapeutic agent developed for humans. As the identified genomic mutation in HER2 is identical to the human variant, than logic follows that the therapeutic agent in humans could be effective for the dogs.

NEWStat: Why hasn’t this sort of genomic study been done on canine cancers before now?

WL: Certainly, there are canine cancer genomic studies that have been published. What makes this [study] different is the presence of a lung cancer mutation in the dog that is identical to the mutation found in humans with never-smoker lung cancer.

We are now at a point where genomics tools from the human world are lifted over to the canine genome; up until this time, we had limited capabilities to deep sequence the canine genome.

NEWStat: What makes the upcoming clinical trial different from other clinical trials?

WL: The upcoming trial is the first precision-medicine clinical trial for dogs with lung cancer. That is, the selection of cancer therapy for a particular patient is based on the genomic profile of the patient's tumor and matched with agents that are known to [specifically] target the identified mutation.

We are particularly excited about our first-of-a-kind canine liquid biopsy assay that provides a noninvasive method to determine if the lung cancer patient has the specific HER2 mutation we are interested in treating.

Lorch says they’ll be enrolling dogs in the clinical study for the next year.

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