This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: A benign but invasive canine oral cancer is often mistaken for a similar malignant one, leading to misdiagnoses in close to a third of cases. But a new diagnostic tool can now distinguish between the two, according to a new study that also identified a promising FDA-approved drug ready for clinical trials.
Canine acanthomatous ameloblastoma (CAA) is a benign but locally aggressive, destructive and invasive tumor that is relatively common in dogs. Surgery is the standard treatment, often involving removal of a section of the jawbone. Many features of CAA overlap with canine oral squamous cell carcinoma (COSCC), a malignant, metastatic canine oral cancer, making it challenging for clinicians to distinguish between the two.
The multidisciplinary research team used advanced high-resolution genomic techniques to isolate and profile single cells from tumor samples and identify a rare cell type unique to CAA, making it possible to more clearly differentiate between the two cancers. They also discovered that these rare cells express a gene called ERBB4, which belongs to a family of well-studied genes important in many human cancers, including certain forms of breast cancer. The team found that an FDA-approved drug targeting ERBB4 showed promising results in reducing CAA tumor growth, opening the door for clinical trials in dogs.
The research resulted from the wide variety of expertise and advanced tools found at Cornell. "Now, with the advent of novel therapies, we are trying to not have to remove large portions of anatomy but instead shrink the tumors to a point where we can do minimal or no surgery at all," said Dr. Santiago Peralta, associate professor of dentistry and oral surgery in the Department of Clinical Sciences in the College of Veterinary Medicine (CVM), and a senior author of the study.
"That's when it becomes super critical to have an absolutely accurate diagnosis because one molecule will be effective in one tumor but not in the other." "There's no way this could have been done without extensive collaboration across disciplines," said Praveen Sethupathy, professor of physiological genomics and chair of the Department of Biomedical and Translational Sciences in CVM, and a senior author of the paper. Andreas Stephanou, a doctoral student, is the first author of the study, which was published in the journal Molecular Therapy Oncology. Stephanou works with Sethupathy and Iwijn De Vlaminck, professor at the Meinig School of Biomedical Engineering in Cornell Duffield Engineering, and a co-author of the paper.
While Peralta is a clinician with experience diagnosing and treating CAA and COSCC and setting up clinical trials, Sethupathy's lab brings genomic expertise, and Bill Katt, a senior scientist in the Department of Biomedical and Translational Sciences, lent his extensive knowledge of cell models of these cancers. The team wanted to see if they could locate rare cell types in CAA that are often critical in cancer but can go unnoticed depending on the method used to detect them. Peralta provided biopsy specimens from his lab, which Sethupathy, Stephanou and Bo Shui, a senior scientist in Sethupathy's lab, processed and analyzed using single-cell RNA sequencing technology, in which individual cells are separated and molecularly assessed.
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