Ardura Juan A, Álvarez-Carrión Luis, Gutiérrez-Rojas Irene, Alonso Verónica
Bone Physiopathology laboratory, Applied Molecular Medicine Institute (IMMA), Universidad San Pablo-CEU, CEU Universities, Campus Monteprincipe, 28925 Alcorcón, Madrid, Spain.
Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, Campus Monteprincipe, 28925 Alcorcón, Madrid, Spain.
Cancers (Basel). 2020 Apr 25;12(5):1071. doi: 10.3390/cancers12051071.
Advanced prostate cancers that progress to tumor metastases are often considered incurable or difficult to treat. The etiology of prostate cancers is multi-factorial. Among other factors, de-regulation of calcium signals in prostate tumor cells mediates several pathological dysfunctions associated with tumor progression. Calcium plays a relevant role on tumor cell death, proliferation, motility-invasion and tumor metastasis. Calcium controls molecular factors and signaling pathways involved in the development of prostate cancer and its progression. Such factors and pathways include calcium channels and calcium-binding proteins. Nevertheless, the involvement of calcium signaling on prostate cancer predisposition for bone tropism has been relatively unexplored. In this regard, a diversity of mechanisms triggers transient accumulation of intracellular calcium in prostate cancer cells, potentially favoring bone metastases development. New therapies for the treatment of prostate cancer include compounds characterized by potent and specific actions that target calcium channels/transporters or pumps. These novel drugs for prostate cancer treatment encompass calcium-ATPase inhibitors, voltage-gated calcium channel inhibitors, transient receptor potential (TRP) channel regulators or Orai inhibitors. This review details the latest results that have evaluated the relationship between calcium signaling and progression of prostate cancer, as well as potential therapies aiming to modulate calcium signaling in prostate tumor progression.
进展为肿瘤转移的晚期前列腺癌通常被认为无法治愈或难以治疗。前列腺癌的病因是多因素的。在其他因素中，前列腺肿瘤细胞中钙信号的失调介导了与肿瘤进展相关的几种病理功能障碍。钙在肿瘤细胞死亡、增殖、运动侵袭和肿瘤转移中发挥着相关作用。钙控制着参与前列腺癌发生发展及其进展的分子因子和信号通路。这些因子和通路包括钙通道和钙结合蛋白。然而，钙信号在前列腺癌骨嗜性易感性方面的作用相对未被充分探索。在这方面，多种机制触发前列腺癌细胞内钙的瞬时积累，可能有利于骨转移的发展。前列腺癌的新疗法包括以靶向钙通道/转运体或泵的强效和特异性作用为特征的化合物。这些用于治疗前列腺癌的新型药物包括钙ATP酶抑制剂、电压门控钙通道抑制剂、瞬时受体电位（TRP）通道调节剂或奥拉帕尼抑制剂。本综述详细介绍了评估钙信号与前列腺癌进展之间关系的最新结果，以及旨在调节前列腺肿瘤进展中钙信号传导的潜在疗法。
