Treatment combating human breast cancer works for dogs with lung cancer, too!
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 a type of canine lung cancer. The same gene — HER2 — that causes breast cancer in women also appears to cause canine pulmonary adenocarcinoma, or CPAC, according to a study of pet dogs led by TGen and The Ohio State University. CPAC is the most common lung cancer
in dogs. Neratinib inhibits a mutant cancer-causing form of the HER2, which is common to both CPAC and HER2-positive human breast cancer patients. Published August 20 in the journal Clinical Cancer Research, this study could have significant implications for people who have never smoked. Like many humans who have never smoked, dogs still get lung cancer. “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. 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.” 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.
MORE GOOD NEWS FOR BOTH ENDS OF THE LEASH
Study reveals genetic similarities of osteosarcoma between dogs and children
A bone cancer known as osteosarcoma is genetically similar in dogs and human children, according to the results of a study by TGen and Tufts University. The findings could help break the logjam in the treatment of this deadly disease, which hasn’t seen a significant medical breakthrough in nearly three decades. “While osteosarcoma (OS) is rare in children, it is all too common in many dog breeds, which makes it a prime candidate for the kind of comparative cancer biology studies that could enhance drug development for both children and our canine friends,” said Dr. Will Hendricks, an Assistant Professor in TGen’s Integrated Cancer Genomics Division, and one of the study’s senior authors. Using multiple molecular-level testing platforms, TGen and Tufts researchers sequenced the genomes of 59 dogs, finding that canine OS shares many of the genomic features of human OS, including low mutation rates, structural complexity, altered cellular pathways, and unique genetic features of metastatic tumors that spread to other parts of the body. Study results appeared July 19 in the Nature publication, Communications Biology. OS is an aggressive disease and the most commonly-diagnosed primary bone tumor in dogs and children. Though a relatively rare cancer in humans — with fewer than 1,000 cases each year — OS strikes more than 25,000 dogs annually. Although surgery and chemotherapy can extend survival, about 30 percent of pediatric OS patients die from metastatic tumors within 5 years. The cancer moves
much faster in dogs, with more than 90 percent succumbing to metastatic disease within
2 years.
