The therapeutic potential of targeting ABC transporters to combat multi-drug resistance.
Most disseminated cancers remain fatal despite the availability of a variety of conventional and novel treatments including surgery, chemotherapy, radiotherapy, immunotherapy, and biologically targeted therapy. A major factor responsible for the failure of chemotherapy in the treatment of cancer is the development of multidrug resistance (MDR). The overexpression of various ABC transporters in cancer cells can efficiently remove the anticancer drug from the cell, thus causing the drug to lose its effect. Areas covered: In this review, we summarised the ongoing research related to the mechanism, function, and regulation of ABC transporters. We integrated our current knowledge at different levels from molecular biology to clinical trials. We also discussed potential therapeutic strategies of targeting ABC transporters to reverse MDR in cancer cells. Expert opinion: Involvement of various ABC transporters to cancer MDR lays the foundation for developing tailored therapies that can overcome MDR. An ideal MDR reversal agent should have broad-spectrum ABC-transporter inhibitory activity, be potent, have good pharmacokinetics, have no trans-stimulation effects, and have low or no toxicity. Alternatively, nanotechnology-based drug delivery systems containing both the cytotoxic drug and reversing agent may represent a useful approach to reversing MDR with minimal off-target toxicity.
a School of Science , Auckland University of Technology , Auckland , New Zealand.
Piyush
P
Bugde
a School of Science , Auckland University of Technology , Auckland , New Zealand.
Riya
R
Biswas
a School of Science , Auckland University of Technology , Auckland , New Zealand.|b School of Science, AUT Roche Diagnostic Laboratory , Auckland University of Technology , Auckland , New Zealand.
Fabrice
F
Merien
a School of Science , Auckland University of Technology , Auckland , New Zealand.|c School of Interprofessional Health Studies , Auckland University of Technology , Auckland , New Zealand.
Jun
J
Lu
a School of Science , Auckland University of Technology , Auckland , New Zealand.
Dong-Xu
DX
Liu
d Department of Respiratory Medicine , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , China.
Mingwei
M
Chen
e Department of Biotechnology and Bioengineering , College of Chemical Engineering, Huaqiao University , Xiamen , China.
Shufeng
S
Zhou
a School of Science , Auckland University of Technology , Auckland , New Zealand.|c School of Interprofessional Health Studies , Auckland University of Technology , Auckland , New Zealand.
Yan
Y
Li
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036103:Nanotechnology; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents
ABC transporter; cancer; multidrug resistance; nanotechnology; pharmacokinetics