[Drug resistance mediated by ABC transporters].
Remarkable advances have been made in cancer chemotherapy by developing new anticancer drugs and pharmacogenomics strategies. However, multidrug resistance in human cancers is the major obstacle to long-term, sustained patient response to chemotherapy. Several ATP-binding cassette (ABC) transporters cause multidrug resistance in cancer cells by actively extruding the clinically administered chemotherapeutic drugs. P-glycoprotein (ABCB1/MDR1/P-gp) and MRP1 (ABCC1/GS-X pump) have been well characterized in terms of their molecular structure and function. In addition, ABCG2/breast cancer resistance protein (BCRP) is the most recently identified/ABC transporter, and is also reportedly associated with cellular resistance against chemotherapeutic agents, such as DNA topoisomerase I, II inhibitor. It is important to note that these ABC transporters are expressed not only in cancer cells but also in normal tissues to play a pivotal role in the absorption, distribution, and excretion of endogenous substances as well as xenobiotics. ABC transporters are key factors that can affect the pharmacokinetic profiles of drugs. Recent studies have revealed that many single nucleotide polymorphisms (SNPs) reside in these ABC transporter genes. Functional analysis of the genetic polymorphism of ABC transporters would greatly contribute to our understanding of individual differences in the drug response and also to the development of personalized medicine in the near future.
Yoshikawa
Megumi
M
Dept. of Drug Metabolism and Disposition, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo 204-8588, Japan.
Ito
Akiko
A
Ishikawa
Toshihisa
T
Ikegami
Yoji
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D019450:Genes, MDR; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000502:physiology; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011110:Polymorphism, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C116614:ABCG2 protein, human; C114462:multidrug resistance-associated protein 3; C421109:multidrug resistance-associated protein 1