PHOENIX, Ariz. -- Aug. 20, 2019 -- Despite those velvet paintings of poker-playing dogs smoking pipes, cigars and cigarettes, our canine friends really don't use tobacco. But like many humans who have never smoked, dogs still get lung cancer.
And, like many women who develop a particular type of breast cancer, the same gene -- HER2 -- also appears to be the cause of lung cancer in many dogs, according to a promising new study of pet dogs led by the Translational Genomics Research Institute (TGen), an affiliate of the City of Hope, and The Ohio State University.
Published today in the journal Clinical Cancer Research, this study could have significant implications for people who have never smoked.
TGen and Ohio State found that neratinib -- a drug that has successfully been used to battle human breast cancer -- might also work for many of the nearly 40,000 dogs in the U.S. that annually develop the most common type of canine lung cancer, known as canine pulmonary adenocarcinoma, or CPAC.
Neratinib inhibits a mutant cancer-causing form of the gene HER2, which is common to both CPAC and HER2-positive human breast cancer patients.
"With colleagues at Ohio State, we found a novel HER2 mutation in nearly half of dogs with CPAC. We now have a candidate therapeutic opportunity for a large proportion of dogs with lung cancer," said Dr. Will Hendricks, an Assistant Professor in TGen's Integrated Cancer Genomics Division, Director of Institutional Research Initiatives, and the study's senior author.
Based on the results from this study, a clinical trial using neratinib is planned for dogs with naturally occurring lung cancer that have the HER2 mutation.
"This 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 specially target the identified mutation," said Dr. Wendy Lorch, an Associate Professor in the Department of Veterinary Clinical Sciences at The Ohio State University College of Veterinary Medicine, who also will run the study's clinical trial.
"Our team at The Ohio State University has worked for years to find treatments for canine lung cancer. This breakthrough shows the value of these studies for dogs, as well as humans with lung cancer who never smoked," said Dr. Lorch, who also is the study's lead author.
CPAC is an aggressive disease that clinically resembles human lung cancer among never-smokers. There is no standard-of-care treatment for CPAC and -- prior to the work performed by the TGen-Ohio State team -- little was known of the disease's genetic underpinnings.
"These results are the first example of our efforts to adapt genomics tools from the human world, such as gene sequencing and liquid biopsies, to generate novel insights in canine cancers, with mutual benefit for both," said Dr. Muhammed Murtaza, Assistant Professor and Co-Director of TGen's Center for Noninvasive Diagnostics, and one of the study's contributing authors.
While the sequencing of hundreds of thousands of human cancer genomes has driven the transformational development of precise targeted cancer treatments for humans over the past decade, relatively few canine cancer genomes have undergone similar profiling. The canine cancer genomic discovery and drug development efforts of the TGen-Ohio State team are pieces of a larger puzzle that could similarly transform veterinary oncology, while creating bridges between canine and human cancer drug development.
"This study is groundbreaking because it not only identified a recurring mutation in a canine cancer that had never been found before, but it actually led directly to a clinical trial," said Dr. Jeffrey Trent, TGen President and Research Director, and one of the study's contributing authors. "This clinical translation from dog to human and back is the holy grail of comparative cancer research."
Lung cancer is the leading cause of cancer death in the U.S., annually taking the lives of more than 154,000 Americans.
"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. 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 canine cancers," Dr. Hendricks added.
No dogs were harmed in this study. Only pet dogs with naturally occurring cancer were examined.
This study -- Identification of recurrent activating HER2 mutations in primary canine pulmonary adenocarcinoma -- lays the foundation for potential rapid translational development. Follow-up clinical and genomic studies have been funded in part by a $300,000 grant investment from the Petco Foundation made possible through their 10-year Pet Cancer Campaign in partnership with Blue Buffalo. Susanne Kogut, President of The Petco Foundation, said her organization's investment in the next phase of TGen-Ohio State studies is part of a larger effort to improve the health and welfare of pets everywhere.
"We are so excited to be a part of this study of canine lung cancer, which we hope will rapidly benefit our pet, and pet-parent, communities worldwide," said Kogut, who in 2016 was named one of 25 "women of influence" by Pet Age magazine.
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Additional funding for the study published today in Clinical Cancer Research came from: the National Cancer Institute, National Canine Cancer Foundation, Bisgrove Scholars Program, Brooke's Blossoming Hope, private donations to the TGen Foundation, and the National Institutes of Health through its Clinical and Translational Science Awards Program (CTSA).
Puma Biotechnology is providing neratinib for the upcoming clinical trial.
About TGen, an affiliate of City of Hope
Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life-changing results. TGen is affiliated with City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases: http://www.cityofhope.org. This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. TGen is focused on helping patients with neurological disorders, cancer, diabetes and infectious diseases through cutting-edge translational research (the process of rapidly moving research toward patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and complex rare diseases in adults and children. Working with collaborators in the scientific and medical communities worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. For more information, visit: http://www.tgen.org. Follow TGen on Facebook, LinkedIn and Twitter @TGen.
Media Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
syozwiak@tgen.org
About The Ohio State University College of Veterinary Medicine
Founded in 1885, The Ohio State University College of Veterinary Medicine is ranked fifth in the nation and includes more than 1,000 faculty, staff and students. Uniquely located in a heavily populated urban area surrounded by a strong rural and agricultural base, the college's Veterinary Medical Center is among the largest of its kind. Encompassing four hospitals and a large animal practice, the Veterinary Health System provides care for more than 72,000 canine, feline, equine and farm animal patients each year. Located on one of the few campuses in the country with seven health sciences colleges on one university campus, Veterinary Medicine students, researchers and faculty closely collaborate with partners in Dentistry, Medicine, Nursing, Optometry, Pharmacy and Public Health. The college admits up to 162 veterinary students per class, and offers a comprehensive graduate program in Veterinary and Comparative Medicine as well as a unique Master's degree in Veterinary Public Health, in partnership with the College of Public Health. Learn more at http://vet.osu.edu.
About the Petco Foundation
At the Petco Foundation, we believe that every animal deserves to live its best life. Since 1999, we've invested more than $250 million in lifesaving animal welfare work to make that happen. With our more than 4,000 animal welfare partners, we inspire and empower communities to make a difference by investing in adoption and medical care programs, spay and neuter services, pet cancer research, service and therapy animals, and numerous other lifesaving initiatives. Through our Think Adoption First program, we partner with Petco stores and animal welfare organizations across the country to increase pet adoptions. So far, we've helped more than 6 million pets find their new loving families, and we're just getting started. Visit petcofoundation.org to learn more about how you can get involved.
Journal
Clinical Cancer Research