Cancer stem cell and ATP binding cassette. Which role in chemoresistance?

Chemoresistance is mediated through a variety of cellular alterations including, among others, reduced\r\ndrug accumulation, decreased levels of protein targets, change in drugs metabolism, and break down of\r\napoptotic signaling.\r\nThe capability to acquire resistance to multiple compounds by cancer stem cells (CSCs), called multidrug\r\nresistance (MDR), is attributed to overexpression of ATP-binding cassette (ABC) transporters that extrude\r\nseveral substrates from the cell using ATP as driving force.\r\nABC proteins are involved in the exclusion from the cells of several physiological compounds and/or\r\nxenobiotics. Three members of the ABC protein superfamily, ABCB1, ABCC1, and ABCG2 which play\r\na major role in mediating clinical development of the MDR phenotype are also implicated in protection\r\nfrom chemotherapy of CSCs. In brief, the most intriguing characteristic of CSCs is their ability to acquire\r\nresistance to multiple anticancer agents that is often mediated by overexpression of ABC transporters\r\nwhich remove drugs out of the cell against a concentration gradient.\r\nModulation of ABC transporters, using inhibitors in a combination therapy with cytostatic agents, could\r\nbe a winning strategy to mitigate CSCs’ chemoresistance and open the door to apoptotic pathways of these\r\ncells in order to prevent relapse of tumor metastases.