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. (AU)
Articles published in Agência FAPESP Newsletter about the research grant:
DA SILVA, RODRIGO FERNANDES;
CARDOZO, DANIELA MAIRA;
LIBANIO RODRIGUES, GISELE OLINTO;
DE SOUZA-ARAUJO, CAROLINE NATANIA;
MIGITA, NATACHA AZUSSA;
LUCCI DE ANGELO ANDRADE, LILIANA APARECIDA;
YUNES, JOSE ANDRES;
CAISMOV24, a new human low-grade serous ovarian carcinoma cell line.
NOV 13 2017.
Web of Science Citations: 0.
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