The Daniel K. Inouye College of Pharmacy, Department of Pharmaceutical Sciences, University of Hawaii at Hilo, United States.
Department of Oncogenomics, Amsterdam UMC, Amsterdam, the Netherlands.
Cell Calcium. 2019 Sep;82:102052. doi: 10.1016/j.ceca.2019.06.006. Epub 2019 Jun 17.
Neuroblastoma (NB) is the most common extra-cranial pediatric solid tumor in children. Despite NB's relative rarity, high-risk NB patients have a poor prognosis with survival rate less than 50%. This is even worse for patients with relapsed or refractory NB. Finding effective alternative treatment strategies is therefore a must. Calcium is an intracellular messenger that is unequivocally present in normal physiology mediating proliferation, growth, migration, cell division, angiogenesis and cell death, as well as pathophysiological processes such as those included in Weinberg's hallmarks of cancer. Within the past 20 years, the molecular identity of most calcium channels has been revealed, however for some of these channels the precise gating mechanism and their role in normal physiology is still elusive. Here we review the recent findings of components of calcium signaling that are deregulating in the malignant progression of NB. We further integrate critical calcium signaling pathways using patient-derived expression analysis. Revealing the roles of these calcium pathways in tumor development, progression, microenvironment and importantly - protection against antineoplastic drugs may hopefully lead to novel treatment strategies in the future.
神经母细胞瘤（NB）是儿童中最常见的颅外小儿实体瘤。尽管 NB 相对罕见，但高危 NB 患者的预后较差，生存率低于 50%。对于复发或难治性 NB 患者，情况更糟。因此，寻找有效的替代治疗策略是必要的。钙是一种细胞内信使，在正常生理过程中广泛存在，介导增殖、生长、迁移、细胞分裂、血管生成和细胞死亡，以及包括 Weinberg 癌症特征在内的病理生理过程。在过去的 20 年中，大多数钙通道的分子特性已经被揭示，然而对于其中一些通道，其精确的门控机制及其在正常生理中的作用仍然难以捉摸。在这里，我们回顾了钙信号传导成分在 NB 恶性进展中失调的最新发现。我们进一步整合了基于患者衍生表达分析的关键钙信号通路。揭示这些钙途径在肿瘤发生、进展、微环境中的作用，以及 - 对抗肿瘤药物的保护作用，有望为未来带来新的治疗策略。
