Lapatinib effects on HER2+ and HER2- canine mammary carcinoma cells cultured in vitro

Author(s)

Antonio Fernando Leis Filho

• Document type: Master's Dissertation
• Press: Botucatu. 2020-09-01.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Medicina Veterinária e Zootecnia. Botucatu
• Defense date: 2020-08-28
• Advisor: Renée Laufer Amorim; Carlos Eduardo Fonseca Alves

Abstract

HER2 is a prognostic and predictive marker widely used in breast cancer diagnosis in women and its overexpression is linked to shorter disease-free survival, decreased expression of estrogen and progesterone receptors, higher proliferation rate and cell migration, tumor invasiveness, frequency of metastases, angiogenesis and decreased apoptosis. In the mammary neoplasms of dogs, the role of HER2 is not yet satisfactorily clarified, however it has already been observed that its overexpression is related to cellular pleomorphism and increased numbers of mitosis figures. This relationship has also been noticed in women. Lapatinib is a tyrosine kinase inhibitor that acts by blocking the phosphorylation of HER2 receptors. Its use is linked to better results in the treatment of women with HER2+ tumors. The aim was to access the effects of lapatinib on primary and metastatic canine mammary gland carcinoma cell cultures in vitro. Cell cultures from four primary mammary carcinoma and two metastases that were previously established and characterized were expanded, treated with lapatinib at concentrations of 0.1, 0.5, 1 and 3µM, for 24h, and had their inhibitory concentration of 50% of the cells (IC50) determined. In addition, we verified the expression of HER2 from all cell cultures. The IC50 of the cells ranged from 0.01 to 0.58 µM. Furthermore, lapatinib was able to inhibit the viability of all treated cell cultures The higher the expression of HER2 in a culture the more sensitive it was to lapatinib. Therefore, treatment with lapatinib can be a promising option for canine patients with primary or metastatic mammary gland carcinoma and can be used especially in animals with HER2+ neoplasms (AU)

• FAPESP's process: 18/14041-4 - Lapatinib effects on Her2+ and Her2- canine mammary carcinoma cells cultured in vitro
• Grantee: Antonio Fernando Leis Filho
• Support Opportunities: Scholarships in Brazil - Master