Expert opinion on therapeutic targets · 2008
ABCA2 as a therapeutic target in cancer and nervous system disorders.
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Mack Jody T, Brown Carol B, Tew Kenneth D
Аннотация
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.
RESULTS/CONCLUSION: 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.
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.
RESULTS/CONCLUSION: 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.