Evaluation of the in vitro and in vivo effect of tellurium (Te) compounds in therapy for canine oral mucosal melanoma, with and without association with carboplatin.

• Grant number: 24/00114-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: November 01, 2024
• End date: February 29, 2028
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Maria Lucia Zaidan Dagli
• Grantee: Érica Thurow Schulz
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Oral mucosal melanomas (OMM) are very common and aggressive neoplasms in dogs. Treatment options for MMO include surgery, chemotherapy, radiotherapy and immunotherapy, however, relapses and metastases are frequent due to rapid evolution and multiple drug resistance (MDR). Therefore, new therapies are being researched and tellurium (Te) compounds have demonstrated effectiveness, one of the mechanisms of action being the inhibition of the activity of MDR efflux pumps. The objective of this project is to evaluate the in vitro and in vivo effect of Te compounds on different cell lines of canine oral mucosa melanomas, with and without association with carboplatin. To this end, canine MMO cells from the TLM1, CMGD2 and CMGD5 lineages will be cultured and treated with different concentrations of Te compounds in different "hits" (Te-13, Te-18 and Te-24) and will be evaluated for cell viability. , cell death, clonogenic and migration capacity and inhibition of expression of the P-glycoprotein (P-gp) efflux pump. The compound(s) that show the best results will be evaluated in combination with carboplatin. In vivo trials in immunodeficient mice xenotransplanted with canine MMO lines will be carried out with the formulations and concentrations of Te that show promise, with and without association with carboplatin. In this way, it is expected to establish new precision therapies for these neoplasms.