Exosomes-mediate microRNAs transfer in breast cancer chemoresistance regulation

Abstract

Breast cancer is the most common and fatal type of cancer in women worldwide due to the metastatic process and resistance to treatment. Despite advances in molecular knowledge, little is known regarding resistance to chemotherapy. One highlighted aspect is the DNA damage response (DDR) pathway that is activated upon genotoxic damage, controlling the cell cycle arrest or DNA repair activation. Recently, studies have showed that cancer stem cells (CSCs) could promote chemoresistance through DDR pathway. Furthermore, it is known that the epithelial-mesenchymal transition (EMT) can generate cells with CSCs characteristics and therefore regulate the chemoresistance process. The exosomes are microvesicles filled with RNAs, proteins and microRNAs (miRNAs) that can be released by many cell types, including tumor cells and CSCs. The exosomes content may be cell-to-cell transferable and it could control a wide range of pathways during tumor development and metastasis. A big challenge for modern medicine is to determine the reasons why patients do not respond to chemotherapy treatments and also guide the most appropriate therapy for each one. Considering that the CSCs are able to stimulate the formation of a more aggressive tumor phenotype with migration and metastasis ability, resistance to treatment and disease recurrence, as well as few studies capable to determine clearly the interaction of breast CSCs with its microenvironment, the present review summarize the possibility that exosomes-mediate miRNAs transfer and regulate chemoresistance in breast tumor cells and CSCs, to clarify the complexity of breast cancer progression and therapy.

Keywords: Breast cancer; chemoresistance; exosomes; microRNAs.