Role in Multidrug Resistance
ABC transporters are known to play a crucial role in the development of multidrug resistance (MDR). In MDR, patients that are on medication eventually develop resistance not only to the drug they are taking but also to several different types of drugs. This is caused by several factors, one of which is increased excretion of the drug from the cell by ABC transporters. For example, the ABCB1 protein (P-glycoprotein) functions in pumping tumor suppression drugs out of the cell. Pgp also called MDR1, ABCB1, is the prototype of ABC transporters and also the most extensively-studied gene. Pgp is known to transport organic cationic or neutral compounds. A few ABCC family members, also known as MRP, have also been demonstrated to confer MDR to organic anion compounds. The most-studied member in ABCG family is ABCG2, also known as BCRP (breast cancer resistance protein) confer resistance to most of Topoisomerase I or II inhibitors such as topotecan, irinotecan, and doxorubicin.
It is unclear exactly how these proteins can translocate such a wide variety of drugs, however one model (the hydrophobic vacuum cleaner model) states that, in P-glycoprotein, the drugs are bound indiscriminately from the lipid phase based on their hydrophobicity.
Read more about this topic: ATP-binding Cassette Transporter
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