Identification of molecular targets asscociated with resistance to antitumor drugs Carboplatin and Rebeccamycin analogues using Saccharomyces cerevisiae as model cell

• Grant number: 11/04173-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2011
• End date: July 31, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Gisele Monteiro
• Grantee: Graziele Fonseca de Sousa
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 09/01303-1 - Characterization of unknown function ORFs involved in Saccharomyces cerevisiae antioxidant response, AP.JP

Abstract

There is great interest from pharmaceutical companies in finding an appropriate treatment for patients with cancer which presented resistance to drugs commonly used to fight the cancer. Therefore, it is necessary to search for new genetic markers that are associated with the patient's predisposition to react differently than expected to the drug effect. For this purpose, several studies have been developed, based in anticancer drugs. Among these medicines, we may highlight the antitumor drug rebeccamycin that has the ability to inhibit the catalytic action of topoisomerases I and II, and the chemotherapeutic agents platinum-based, such as carboplatin, cisplatin and oxaliplatin, which act by eliminating cancer cells through the formation of adducts with purine bases of DNA. Thus, this project has the prospect of finding yeast mutants resistant to carboplatin and rebeccamycin analogues. These mutants will be exposed to different concentrations of these drugs and after the identification of resistant phenotypes, there will be the identification and molecular characterization of genes involved in the process. This proposal aims to find the genes responsible for resistance to these antitumor drugs, making it possible to develop a more individualized therapy for each patient, giving a better life expectancy. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE SOUSA, GRAZIELE FONSECA; LIMA, MAIRA DE ASSIS; CUSTODIO, DEBORA FERNANDES; FREITAS, VANESSA MORAIS; MONTEIRO, GISELE. Chemogenomic Study of Carboplatin in Saccharomyces cerevisiae: Inhibition of the NEDDylation Process Overcomes Cellular Resistance Mediated by HuR and Cullin Proteins. PLoS One, v. 10, n. 12, DEC 21 2015. (11/04173-1, 09/01303-1, 15/07749-2)

DE SOUSA, GRAZIELE FONSECA; WLODARCZYK, SAMARINA RODRIGUES; MONTEIRO, GISELE. Carboplatin: molecular mechanisms of action associated with chemoresistance. Brazilian Journal of Pharmaceutical Sciences, v. 50, n. 4, p. 693-701, OCT-DEC 2014. (09/01303-1, 11/04173-1)