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News Article

Precision medicine canine lung cancer study


Dogs with lung cancer may get gene-directed treatment with the same drug used to combat a type of human breast cancer

Researchers have found that neratinib — a drug that has successfully been used to treat human breast cancer — might also work for the most common type of canine lung cancer, canine pulmonary adenocarcinoma (CPAC). The study, led by the Translational Genomics Research Institute (TGen), an affiliate of the City of Hope, and The Ohio State University, is published in Clinical Cancer Research.

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 tumour 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. Jeff 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.”

Article: Lorch, G.; Sivaprakasam, K.; Zismann, V. L. ;Perdigones, N.; Contente-Cuomo, T.; Nazareno, A.; Facista, S. J.; Wong, S.; Drenner, K.; Liang, W. S.; Amann, J. M.; Sinicropi-Yao, S. L.; Koenig, M. J.; LaPerle, K.; Whitsett, T. G.; Murtaza, M.; Trent, J. M.; Carbone, D. P.; Hendricks, W. P. D. (2019). Identification of recurrent activating HER2 mutations in primary canine pulmonary adenocarcinoma. Clinical Cancer Research, published OnlineFirst 20 August 2019, doi: 10.1158/1078-0432.CCR-19-1145

Article details

  • Date
  • 21 August 2019
  • Source
  • Translational Genomics Research Institute
  • Subject(s)
  • Dogs, Cats, and other Companion Animals