Introduction
Breast cancer resistance protein (BCRP or ABCG2) is an efflux transporter that belongs to the ABC superfamily (ATP-binding cassette). It is encoded by the gene first isolated from breast cancer cells in 1998. BCRP consists of 655 amino acids and has a molecular weight of 72 kDa. BCRP mediates resistance to structurally and pharmacologically diverse cytostatic drugs in cancer cells by “pumping” them out of the cancer cells. This means that the anticancer drugs cannot enter the cells and exert their pharmacologic effects.
Transport mechanism
BCRP is an active efflux transporter that transports its substrates from the cell membrane, where it is localized, back to the outside space. This transport is also possible against a concentration gradient because of the use of energy from ATP.
Substrates
BCRP has very broad substrate specificity and therefore can transport many different substances, including numerous pharmaceutical agents. These include, for example, antiviralia, quinolones, statins, various cytostatic drugs, and kinase inhibitors.
Occurrence and function
BCRP is not only found in cancer cells but is a physiological transporter found at many organs, including the intestine, liver, blood–brain barrier, placenta, and kidney. It is thought to be a protective mechanism that protects the body and cells from harmful substances by forming a barrier against them and promoting their elimination from the organism. In addition, other physiological functions exist.
Significance for drug therapy
Because BCRP is a barrier to pharmaceutical agents, BCRP substrates may reach their site of action inadequately. This is the case with so-called multidrug resistance (MDR), or resistance of cancer cells to chemotherapeutic agents (see above). BCRP substrates are susceptible to drug-drug interactions. When they are co-administered with a BCRP inhibitor such as ketoconazole or HIV protease inhibitors, concentrations in the body increase. This increases the risk for adverse effects.