Calcium signaling regulates fundamental processes involved in Neuroblastoma progression

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.