# Mapping the Kinase Inhibitor Landscape in Canine Mammary Carcinoma: Current Status and Future Opportunities

## TL;DR

This paper reviews the limited use of human-approved kinase inhibitors in treating canine mammary cancer, highlighting the potential for translational research to benefit both veterinary and human medicine.

## Contribution

The paper identifies conserved kinase pathways in canine and human mammary cancer and proposes translational research strategies to evaluate existing drugs for veterinary use.

## Key findings

- Key kinase signaling pathways are conserved between canine and human mammary carcinomas.
- In vitro studies show that drugs like palbociclib and alpelisib inhibit growth in canine mammary cancer cell lines.
- No clinical trials have been conducted in dogs despite preclinical evidence of drug activity.

## Abstract

Canine mammary cancer is one of the most common cancers in females. In humans, drugs that block enzymes responsible for cell division, called kinases, have become an essential part of modern treatment, significantly improving survival. These drugs, approved for human use, can generally be adapted for veterinary use without the need to develop entirely new compounds. However, this article demonstrates that only a small number of these kinase inhibitors have been tested or used in dogs, despite evidence that the same biological pathways drive cancer growth in both species. To make the necessary progress, additional laboratory studies are needed to confirm the safety and activity of these drugs in canine cancer models, such as cell cultures and xenotransplantation, and to corroborate these findings in randomised clinical trials in dogs with spontaneous mammary cancer.

Background: Canine mammary carcinoma (CMC) is the most common malignant tumour in female dogs and, due to its similarities, is a valuable comparative model for human breast cancer. Kinase inhibitors have revolutionised the treatment of human breast cancer; their use in veterinary oncology remains marginal. Aim: This review summarises the current knowledge of kinase signalling pathways in CMC and assesses which kinase inhibitors approved for human use have potential in veterinary medicine. Methods: A systematic search of the PubMed database from 1985 to 2025 was performed, focusing on kinase-targeted therapies in both human and canine mammary carcinomas. Data were categorised according to molecular target, clinical approval status, and available preclinical or clinical veterinary evidence. Results: Key molecular pathways targeted by kinase inhibitors are conserved across species, supporting translational opportunities. In vitro studies demonstrate that palbociclib, alpelisib, everolimus, and lapatinib inhibit growth and signalling in CMC cell lines. Clinical trials have not been conducted. Conclusions: Approved kinase inhibitors for human use have untapped therapeutic potential in veterinary oncology. Translational research, including xenograft and organoid models, followed by clinical trials in dogs, is required. Gaining this knowledge could lead to targeted treatment for dogs while advancing comparative understanding of mammary cancer biology across species.