Chemotherapy remains the principal mode to treat many metastatic cancers. However, sooner or later, cancer patients may develop multidrug resistance (MDR). Occurrence of cellular MDR prevents efficient killing of the cancer cells, leading to chemotherapeutic treatment failure. Thus, MDR is one of the major obstacles to the successful chemotherapeutic treatment of cancer patients.
Numerous mechanisms of MDR exist in cancer cells, such as “intrinsic” and “acquired” MDR. “Acquired” MDR indicates the fact that some cancers, such as breast cancer, ovarian cancer, non-Hodgkin’s lymphoma, adult acute leukemias and numerous childhood cancers, initially respond to the chemotherapeutic treatment, but eventually become MDR. Over-expression of anti-apoptotic factors, such as Bcl-2 protein, and/or ATP-binding cassette transporters, including P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance protein (MRP1), confers “acquired” MDR. However, the mechanisms of the MDR caused by these factors are different. For example, over-expression of Bcl-2 protein inhibits the intrinsic apoptosis pathway and results in decreased sensitivity to anticancer drugs. In contrast, ATP binding cassette transporters, including P-gp, BCRP and MRP1, couple ATP binding/hydrolysis to anticancer drug transport and result in decreased intracellular drug concentration such that it is too low to kill the cancer cell. Thus, specific approaches should be applied in order to combat MDR caused by different factors.
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