January 02, 2020
3 min read
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Gene-directed therapy may benefit dogs with lung cancer

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William P.D. Hendricks, PhD
William P.D. Hendricks

Researchers at Translational Genomics Research Institute and The Ohio State University have identified a novel HER2 mutation in dogs with canine pulmonary adenocarcinoma, suggesting that neratinib may benefit dogs with HER2-associated lung cancer.

Results from this study have laid the groundwork for a clinical trial of neratinib (Nerlynx, Puma Biotechnology), an irreversible pan-HER tyrosine kinase inhibitor that has demonstrated efficacy in human breast cancer, for dogs with naturally occurring lung cancer that carry the HER2 mutation.

“This study is really exciting to us because, not only have we found a recurrent hot-spot mutation in a canine cancer that had never been found before, but it actually has direct clinical translational relevance,” William P.D. Hendricks, PhD, assistant professor in TGen’s Integrated Cancer Genomics Division, said in a press release. “For humans, we already have drugs that can inhibit many dysregulated proteins. We hope to show that we can provide the same benefit for dogs with cancer.”

Healio spoke with Hendricks about what prompted this study, the results and plans for additional research.

Question: What prompted this research ?

Answer : My lab focuses on research in comparative oncology, which considers the convergent needs and opportunities of studying the genetic basis of naturally occurring cancer in dogs, as well as the drug development needs of humans with cancer. No dogs are harmed in our studies. All of our research is with pets with spontaneous disease. Considering that the cost of developing a successful anticancer drug for humans is in the range of $2.5 billion, we believe that incorporating the study of naturally occurring cancer in pet dogs can help reduce that cost and meet the needs of both dogs and humans. There are many similarities between the species. Canine cancer occurs over the course of years, much like human cancer. It develops in the setting of an intact immune system, unlike many mouse models. And, dogs share our environment, so there is convergence there, as well. Many other features help align the clinical needs of humans and dogs. For example, just like people who have never smoked, dogs still get lung cancer. We believe we can learn lessons from the genetic underpinnings of this cancer in dogs that we might apply to humans with lung cancer who have never smoked. More than 4 million cancer diagnoses occur among dogs in the U.S. each year. The standard of care for many canine cancers is poorly developed. We do not know nearly as much about dogs with cancer as we do about humans with cancer. We are looking to change this paradigm.

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Q: How did you conduct the study?

A: We have common interests with our key collaborator at The Ohio State University, Gwendolen Lorch, DVM, PhD, associate professor in the department of veterinary clinical sciences at The Ohio State University College of Veterinary Medicine. We aligned the study of lung cancer in pet dogs with needs for better clinical treatments for humans who have never smoked and yet are diagnosed with lung cancer. In partnership with Dr. Lorch, we assembled a clinically annotated retrospective cohort of lung cancer in dogs. We undertook a classic genomic discovery project, developing a gene panel that allowed us to quickly study 88 tumors from dogs with lung cancer.

Q: What did you find?

A: Nearly 40% of the tumors we saw in dogs are driven by the HER2 gene mutation, an important breast cancer gene and one that also shows up in other types of human cancer. This was a striking and exciting finding for us because mapping these genomic landscapes is hugely powerful in helping us figure out how to go about the cross-species alignment. We saw an immediate translational opportunity to treat dogs with the same drug that has been proven to help humans. This was a clear opportunity to evaluate clinical response.

Q: What is next for research on this and when do you expect results to be published?

A: The next step is to study the efficacy of neratinib in HER2-mutant lung cancer in pet dogs. This work is supported by The Petco Foundation and others. We are enthusiastic about opening a clinical trial soon, which will be the first of its kind in many ways. Results probably will be available in about 2 years. – by Jennifer Southall

Reference:

Lorch G, et al. Clin Cancer Res. 2019;doi:10.1158/1078-0432.CCR-19-1145.

For more information:

William P.D. Hendricks, PhD, can be reached at Translational Genomics Research Institute, 445 N. Fifth Street, Phoenix, AZ 85004; email: whendricks@tgen.org.

Disclosure : Hendricks reports serving as a consultant for One Health Co., research funding from Ethos Discovery and travel support from Pathway Vet Alliance.