TY - JOUR
T1 - How to overcome ATP-binding cassette drug efflux transporter-mediated drug resistance?
AU - Jaramillo, Adrian C.
AU - Saig, Farah Al
AU - Cloos, Jacqueline
AU - Jansen, Gerrit
AU - Peters, Godefridus J.
N1 - Publisher Copyright: © The Author(s) 2018. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2018
Y1 - 2018
N2 - P-glycoprotein (ABCB1), multidrug resistance protein-1 (ABCC1) and breast cancer resistance protein (ABCG2) belong to the ATP-binding cassette (ABC) superfamily of proteins that play an important physiological role in protection of the body from toxic xenobiotics and endogenous metabolites. Beyond this, these transporters determine the toxicity profile of many drugs, and confer multidrug resistance (MDR) in cancer cells associated with a poor treatment outcome of cancer patients. It has long been hypothesized that inhibition of ABC drug efflux transporters will increase drug accumulation and thereby overcome MDR, but until now no approved inhibitor of these transporters is available in the clinic. In this review we present molecular strategies to overcome this type of drug resistance and discuss for each of these strategies their promising value or indicate underlying reasons for their limited success.
AB - P-glycoprotein (ABCB1), multidrug resistance protein-1 (ABCC1) and breast cancer resistance protein (ABCG2) belong to the ATP-binding cassette (ABC) superfamily of proteins that play an important physiological role in protection of the body from toxic xenobiotics and endogenous metabolites. Beyond this, these transporters determine the toxicity profile of many drugs, and confer multidrug resistance (MDR) in cancer cells associated with a poor treatment outcome of cancer patients. It has long been hypothesized that inhibition of ABC drug efflux transporters will increase drug accumulation and thereby overcome MDR, but until now no approved inhibitor of these transporters is available in the clinic. In this review we present molecular strategies to overcome this type of drug resistance and discuss for each of these strategies their promising value or indicate underlying reasons for their limited success.
KW - ATP-binding cassette transporters
KW - Breast cancer resistance protein
KW - Multidrug resistance
KW - Multidrug resistance protein
UR - http://www.scopus.com/inward/record.url?scp=85054330308&partnerID=8YFLogxK
U2 - https://doi.org/10.20517/cdr.2018.02
DO - https://doi.org/10.20517/cdr.2018.02
M3 - Review article
SN - 2578-532X
VL - 1
SP - 6
EP - 29
JO - Cancer Drug Resistance
JF - Cancer Drug Resistance
IS - 1
ER -