ATP-binding cassette transporter (focus on ABCB1, ABCG2, and ABCC1) (ABC transporter (specifically: ABCB1, ABCG2, ABCC1))

The ATP-binding cassette (ABC) transporters are a superfamily of transmembrane proteins that mediate the ATP-dependent efflux of a wide variety of substrates, including chemotherapeutic agents, out of cells. Overexpression of these transporters, particularly ABCB1 (P-glycoprotein), ABCG2 (breast cancer resistance protein), and ABCC1 (MRP1), is a major mechanism of multidrug resistance in cancer. Lapatinib, an approved inhibitor of EGFR and HER2 kinases, has been shown to directly interact with and inhibit the efflux function of certain ABC transporters. By inhibiting ABCB1, ABCG2, and ABCC1 function (not expression), lapatinib increases the accumulation of cytotoxic drugs in resistant tumor cells, thereby reversing multidrug resistance both in vitro and in vivo[1][2][3]. However, “Lapatinib on ABC Transporters” is not a specific molecular entity, but rather describes the ability of lapatinib to modulate these transporters.

Other names

P-glycoprotein (ABCB1)Breast cancer resistance protein (ABCG2)Multidrug resistance-associated protein 1 (ABCC1/MRP1)MDR1 (ABCB1)BCRP (ABCG2)MRP1 (ABCC1)

Substrate efflux: ABC transporters use ATP hydrolysis to pump drugs, including chemotherapeutics, out of cells[4][6]. Inhibition by lapatinib: Lapatinib inhibits the function (but not the expression) of ABCB1 and ABCG2 by interacting with their drug-binding or ATP-binding sites, leading to increased intracellular retention of cytotoxic drugs and reversal of multidrug resistance[1][2][3].