Abstract
Early publications using cultured cancer cells immediately recognized the phenomenon of resistance to anticancer agents. However, it was not until 1973 that it was first demonstrated that a major factor in the resistance of cancer cells was that of reduced drug accumulation. This year marks the 30th anniversary of the discovery by Juliano and Ling that P-glycoprotein mediates this active efflux of chemotherapeutic drugs from cancer cells. Since this seminal finding, the investigation of P-glycoprotein (MDR1, ATP binding cassette [ABC]B1) has proceeded with great vigour. However, it soon became apparent that P-glycoprotein was not expressed in all drug-resistant cells that displayed an accumulation deficiency, which led to the discovery of other ABC transporters involved in drug efflux. In 1992, the multidrug resistance-associated protein (MRP1, ABCC1) was identified in small cell lung cancer followed by breast cancer resistance protein (mitoxantrone resistance protein, ABCG2) in 1999. After three decades of research, can we confidently define the contribution of multidrug resistance transporters to chemoresistance and do we have clinically useful drugs to sensitise cancers?
Publication types
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
-
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
-
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
-
ATP Binding Cassette Transporter, Subfamily G, Member 2
-
ATP-Binding Cassette Transporters / antagonists & inhibitors*
-
ATP-Binding Cassette Transporters / genetics
-
ATP-Binding Cassette Transporters / metabolism
-
Animals
-
Antineoplastic Agents / pharmacokinetics
-
Antineoplastic Agents / pharmacology*
-
Antineoplastic Agents / therapeutic use
-
Clinical Trials as Topic
-
Cyclosporins / pharmacology
-
Cyclosporins / therapeutic use
-
Drug Interactions
-
Drug Resistance, Multiple*
-
Drug Resistance, Neoplasm*
-
Humans
-
Imidazoles / pharmacology
-
Imidazoles / therapeutic use
-
Multidrug Resistance-Associated Proteins / antagonists & inhibitors
-
Multidrug Resistance-Associated Proteins / genetics
-
Multidrug Resistance-Associated Proteins / metabolism
-
Neoplasm Proteins / antagonists & inhibitors*
-
Neoplasm Proteins / genetics
-
Neoplasm Proteins / metabolism
-
Neoplasms / drug therapy*
-
Neoplasms / metabolism
-
Quinolines / pharmacology
-
Quinolines / therapeutic use
-
RNA Interference
Substances
-
ABCG2 protein, human
-
ATP Binding Cassette Transporter, Subfamily B, Member 1
-
ATP Binding Cassette Transporter, Subfamily G, Member 2
-
ATP-Binding Cassette Transporters
-
Antineoplastic Agents
-
Cyclosporins
-
Imidazoles
-
Multidrug Resistance-Associated Proteins
-
Neoplasm Proteins
-
OC 144-093
-
Quinolines
-
tariquidar
-
valspodar