Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106
USA

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Targeting ATP7A to Increase the Sensitivity of Neuroblastoma Cells to Retinoid Therapy

Author(s): B. B. Cheung, G. M. Marshall.

Abstract:

Following the discovery that defective retinoid signaling directly contributes to tumorigenesis, and, that retinoids have an anti-cancer effect in vitro and in vivo, retinoids have become part of the routine care in children with neuroblastoma at the stage of minimal residual disease. However, many patients still relapse following retinoid therapy, demonstrating the need for more effective retinoids and better assays to predict retinoid sensitivity in cancer cells. Recent evidence suggests that the copper metabolism gene, ATP7A, is retinoid-regulated and an important component of the retinoic acid receptor β (RARβ) anticancer effect in neuroblastoma cells. To highlight and further develop the concept of using ATP7A as a target in retinoid therapy, and combination therapy with copper chelators in neuroblastoma, the current literature and abstracts related to the clinical application of retinoids, the function of ATP7A and the clinical application of copper chelators are summarized. We propose that strategies targeting the copper export protein, ATP7A, in combination therapy with retinoids and copper depletion therapy, may have great therapeutic potential in the clinical treatment of neuroblastoma and other malignancies.

Keywords: ATP7A, copper chelators, retinoid, retinoic acid, retinoic acid receptor beta, neuroblastoma, N-(4-hydroxyphenyl) retinamide, acute promyelocytic leukemia, retinoid X receptors, copper transporter 1 protein, tripartite motif 16, superoxide dismutase, Copper-resistant Chinese hamster ovary, Tetrathiomolybdate, triethylene tetramine

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Article Details

VOLUME: 11
ISSUE: 7
Year: 2011
Page: [826 - 836]
Pages: 11
DOI: 10.2174/156800911796798968