Analysis of the efficacy of L-asparaginase in inhibiting the metastatic process in human melanoma lineage

• Grant number: 19/26735-3
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): June 01, 2020
• Effective date (End): April 30, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Gisele Monteiro
• Grantee: Carolina Silva
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Melanoma is a malignant skin neoplasm with high plasticity, chemoresistance, and propensity to metastasis. A significant percentage of patients with this disease have BRAFV600E mutation and can be treated with Vemurafenib. Although this drug has an effective initial response, a significant number of patients have tumor resistance and disease progression after a short period of treatment initiation. In a recent study, it was shown that L-asparaginase (ASNase), by decreasing the extracellular availability of the amino acid asparagine, is able to reduce the number of circulating tumor cells and the formation of secondary tumors. Thus, ASNase has the potential for pharmaceutical application in the treatment of patients with solid tumors with high metastatic potential, such as BRAFV600E melanoma. Therefore, the aim of this project is to analyze the efficacy of L-asparaginase in inhibiting the metastatic process in vitro model of BRAFV600E human melanoma. To this end, assays will be performed to evaluate the cytotoxicity of the enzyme ASNase, as well as its effect on colony formation, Vemurafenib resistance acquisition, migration, and cell invasion processes in Vemurafenib sensitive and/or resistant BRAFV600E human melanoma. In the case of ASNase is positively related to metastasis inhibition, the molecular mechanisms involved will be evaluated. (AU)