Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of NSW, Randwick, NSW, Australia.
Curr Cancer Drug Targets. 2011 Sep;11(7):826-36. doi: 10.2174/156800911796798968.
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.
在发现缺陷视黄酸信号直接导致肿瘤发生，以及视黄酸在体外和体内具有抗癌作用之后，视黄酸已成为最小残留疾病阶段神经母细胞瘤患儿常规治疗的一部分。然而，许多患者在接受视黄酸治疗后仍会复发，这表明需要更有效的视黄酸和更好的测定方法来预测癌细胞对视黄酸的敏感性。最近的证据表明，铜代谢基因 ATP7A 是视黄酸调节的，并且是神经母细胞瘤细胞中视黄酸受体 β（RARβ）抗癌作用的重要组成部分。为了强调并进一步发展将 ATP7A 作为视黄酸治疗和神经母细胞瘤中铜螯合剂联合治疗靶点的概念，总结了当前与视黄酸临床应用、ATP7A 功能和铜螯合剂临床应用相关的文献和摘要。我们提出，靶向铜输出蛋白 ATP7A 的策略与视黄酸和铜耗竭治疗联合应用，可能在神经母细胞瘤和其他恶性肿瘤的临床治疗中具有巨大的治疗潜力。
