ABCA2 as a therapeutic target in cancer and nervous system disorders.
BACKGROUND
Overexpression of ATP-binding cassette (ABC) transporters is a major adaptive advantage used by tumor cells to evade the accumulation of cytotoxic agents. ABCA2, a transporter highly expressed in the cells of the nervous and haematopoetic systems, is associated with lipid transport and drug resistance in cancer cells, including tumor stem cells. Recently, a single nucleotide polymorphism (SNP) in Abca2 was linked to early onset Alzheimer's disease (AD). The characterization of two independent knockout mouse models has shed light on putative in vivo functions of this transporter in the development and maintenance of myelin membrane lipids in the CNS.


OBJECTIVE
The objective of this review is to guide the reader through the existing scope of literature on the ABCA2 transporter, focusing on its potential as a future target in human pathologies, specifically cancer and neurological disease.


METHODS
An NCBI PubMed literature search was conducted to address the growing body of ABCA2 literature that, at the time of publication, included 39 reports. From these, we focused on papers that provided insight into the functional importance of this transporter in tumor stem cells, cancer, drug resistance, Alzheimer's disease and myelination.


CONCLUSIONS
These studies have implicated ABCA2 as a therapeutic target in modulating the drug resistance phenotype prevalent in human cancers and in the treatment of neuropathies, including Alzheimer's disease and myelin-related disorders.
Mack
Jody T
JT
Medical University of South Carolina, Department of Cell and Molecular Pharmacology and Experimental Therapeutics, 173 Ashley Avenue, BSB 303, MSC 505, Charleston, South Carolina 29425-5050, USA.
Brown
Carol B
CB
Tew
Kenneth D
KD
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects* / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D009186:Myelin Sheath / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology
C418186:ABCA2 protein, human; D018528:ATP-Binding Cassette Transporters