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MCT1 as a target and response mediator in melanoma therapy

Grant number: 16/10821-0
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): July 01, 2016
Effective date (End): April 30, 2020
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Céline Marques Pinheiro
Grantee:Murilo Queiroz de Almeida Bonatelli
Home Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
Associated research grant:15/25351-6 - MCT1 as a target and response mediator in melanoma therapy, AP.JP

Abstract

In the context of metabolic reprogramming of tumor cells (Warburg effect), several proteins show an increased expression, including monocarboxylate transporters (MCTs). Recently, MCT1 was identified as a major determinant of the sensitivity to 3-bromopyruvate (3-BP), one of the most promising inhibitors of glycolytic metabolism. So, in addition to a potential therapeutic target, MCT1 arises as a response mediator in cancer. Melanoma is the most aggressive form of skin cancer, and studies have shown that BRAF is one of the key oncogenes involved in melanoma tumor genesis. Importantly, BRAF mutations induce the Warburg effect, and this reprogramming of energy metabolism has been identified as a possible strategy for treating melanoma. In this project, following the research that has been developed by the candidate in the last 10 years, the potential of MCT1 as a therapeutic target as well as a mediator of response to treatment with 3-BP as an antineoplastic agent for the treatment of melanoma will be evaluated by using diverse approaches, starting from the characterization of MCT1 expression in tumor samples, through a screening of melanoma cell lines sensitivity to 3-BP and association with MCT1 expression, and characterization of the effect of SLC16A1 (MCT1) knock-out, alone or combined with 3-BP treatment, in tumor aggressiveness characteristics. This project will be developed in close collaboration with researchers from different institutions and aims to open new perspectives for the development of more effective clinical trials in melanoma. (AU)