ANALYSIS OF MOLECULAR BIOMARKERS ASSOCIATED TO CHEMORESISTANCE DERIVED FROM BREAST CANCER STEM CELLS

• Grant number: 15/25056-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2016
• End date: January 31, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Sophie Françoise Mauricette Derchain
• Grantee: Juliana Carvalho Santos
• Host Institution: Centro de Atenção Integral à Saúde da Mulher (CAISM). Hospital da Mulher Professor Doutor José Aristodemo Pinotti. Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Despite advances in molecular knowledge, breast cancer is still the most commonly diagnosed type of cancer and inducing more deaths in women worldwide, mainly due to the metastatic process and resistance to treatment. The DNA damage response pathway (DDR) is activated in response to genotoxic damage, controlling the cell cycle arrest or activating DNA repair. Studies showed that cancer stem cells (CSCs) can promote chemoresistance through DDR. Furthermore, it is known that the epithelial-mesenchymal transition (EMT) can generate cells with stem cells characteristics and therefore regulate the chemoresistance process. The exosomes are microvesicles comprised of RNAs, proteins and miRNAs that can be released by various cell types including tumor cells and CSCs. The exosomes allows the contents transfer cell to cell. Determine the reasons why a patient does not respond to chemotherapy, and thus be able to guide a most appropriate therapy for each patient remains formidable challenge in modern medicine. Fortunately, the genetic content present in circulating blood can provide clues and help change this scenario. We intend to evaluate the possible transfer of miRNAs that regulate chemoresistance among CSCs and tumor cells derived from breast of exosomes in order to understand the complexity of progression and therapy of breast cancer. Considering that the CSCs are able of forming a more aggressive tumor phenotype, with migration ability, metastasis, resistance to treatment and disease recurrence, as well as few studies to determine clearly the interaction of breast CSCs with its microenvironment, we intend to evaluate the possible exosome-mediated miRNAs transfer that regulate chemoresistance of breast CSCs and tumor cells, to help clarify the complexity of progression and therapy of breast cancer.

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)

SANTOS, JULIANA CARVALHO; RIBEIRO, MARCELO LIMA; SARIAN, LUIS OTAVIO; ORTEGA, MANOELA MARQUES; DERCHAIN, SOPHIE FRANCOISE. Exosomes-mediate microRNAs transfer in breast cancer chemoresistance regulation. AMERICAN JOURNAL OF CANCER RESEARCH, v. 6, n. 10, p. 2129-2139, 2016. (15/25056-4)

SANTOS, JULIANA CARVALHO; LIMA, NATALIA DA SILVA; SARIAN, LUIS OTAVIO; MATHEU, ANDER; RIBEIRO, MARCELO LIMA; MAURICETTE DERCHAIN, SOPHIE FRANCOISE. Exosome-mediated breast cancer chemoresistance via miR-155 transfer. SCIENTIFIC REPORTS, v. 8, JAN 16 2018. (15/25056-4, 16/07822-4)