Existing drug shows promise against invasive canine oral tumor

A Cornell University-led research team has developed a diagnostic method to distinguish canine acanthomatous ameloblastoma (CAA), a benign but locally invasive jaw tumor, from canine oral squamous cell carcinoma (COSCC), a malignant cancer that it closely resembles. Misdiagnosis occurs in nearly one-third of cases, leading to overtreatment or undertreatment.

Using single-cell RNA sequencing on biopsy samples, the researchers identified a rare population of cells with a neuron-like molecular signature unique to CAA. These cells express the gene ERBB4, a member of a gene family implicated in several human cancers.

The team then screened a panel of therapeutic compounds on live CAA tumor tissue and found that neratinib, an FDA-approved drug that inhibits ERBB4, effectively suppressed tumor growth. The findings were published in Molecular Therapy Oncology.

Current standard treatment for CAA involves surgical removal of part of the jawbone. Senior author Dr. Santiago Peralta, a veterinary dentist and oral surgeon, said the goal is to shrink tumors with targeted therapy to avoid extensive surgery.

Accurate diagnosis is critical because neratinib would not be effective against the malignant look-alike, COSCC. The multidisciplinary effort combined clinical veterinary expertise, genomic analysis, cell modeling, and systems biology.

Dogs develop CAA relatively frequently, whereas the human analog, adamantinoma, is rare. Researchers note that canine clinical trials can proceed faster than human trials, potentially accelerating treatments for both species.

The work is part of Cornell's Comparative Oral Oncology Laboratory initiative. The team plans to move toward clinical trials in canine patients to test neratinib's efficacy in vivo.