Diagnostic, prognostic and therapeutic approach of HER2 overexpression in canine Mammary Neoplasms

• Grant number: 21/00678-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2021
• End date: February 28, 2025
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Clinics and Surgery
• Principal Investigator: Carlos Eduardo Fonseca Alves
• Grantee: Antonio Fernando Leis Filho
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Mammary Gland Neoplasms are the most common type of cancer in female dogs with half of these being malignant. The life expectancy of animals diagnosed with this disease is generally low. Due to the difficulty in treatment and the high prevalence of Mammary Gland Cancer, the identification of diagnostic, prognostic and therapeutic factors is very important. HER2 is a tyrosine kinase receptor with great relevance in human Breast Neoplasms, and its overexpression is linked to shorter disease-free time, shorter survival, greater cell proliferation and migration, tumor invasion, frequency of metastases, angiogenesis and decrease of apoptosis. In dogs, the relevance of HER2 in these neoplasms is still debated, however, overexpression of HER2 has already been related to increased cell pleomorphism and a greater number of mitosis figures in these animals. Taking this into account, this project aims to validate the use in canine samples of the anti-HER2 antibody used in the immunohistochemistry of human samples by Western blotting and mass spectrometry; correlate the expression of HER2 with the survival of dogs diagnosed with Mammary Gland Cancer; propose and test in vitro a therapy for animals with neoplasms with high HER2 expression using lapatinib in combination with a chemotherapeutic agent to be determined after proteomics of cultured canine mammary carcinoma cell samples treated with lapatinib, in order to complement its effects. (AU)