Institute of Molecular and Translational Cardiology, IRCCS Policlinico San Donato, Piazza Malan 2, 20097 San Donato Milanese, Italy.
School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore, 48, 20900 Monza, Italy.
Int J Mol Sci. 2022 Aug 31;23(17):9894. doi: 10.3390/ijms23179894.
The role of T-type calcium channels is well established in excitable cells, where they preside over action potential generation, automaticity, and firing. They also contribute to intracellular calcium signaling, cell cycle progression, and cell fate; and, in this sense, they emerge as key regulators also in non-excitable cells. In particular, their expression may be considered a prognostic factor in cancer. Almost all cancer cells express T-type calcium channels to the point that it has been considered a pharmacological target; but, as the drugs used to reduce their expression are not completely selective, several complications develop, especially within the heart. T-type calcium channels are also involved in a specific side effect of several anticancer agents, that act on microtubule transport, increase the expression of the channel, and, thus, the excitability of sensory neurons, and make the patient more sensitive to pain. This review puts into context the relevance of T-type calcium channels in cancer and in chemotherapy side effects, considering also the cardiotoxicity induced by new classes of antineoplastic molecules.
T 型钙通道在兴奋细胞中起着重要作用，它们负责产生动作电位、自发性和发射。它们还参与细胞内钙信号转导、细胞周期进程和细胞命运；从这个意义上说，它们也成为非兴奋细胞的关键调节因子。特别是，它们的表达可以被认为是癌症的预后因素。几乎所有的癌细胞都表达 T 型钙通道，以至于它被认为是一个药理学靶点；但是，由于用于降低其表达的药物不是完全选择性的，会出现几种并发症，尤其是在心脏。T 型钙通道也参与了几种作用于微管运输的抗癌药物的特定副作用，增加了通道的表达，从而增加了感觉神经元的兴奋性，使患者对疼痛更敏感。本综述考虑了新型抗肿瘤分子引起的心脏毒性，将 T 型钙通道在癌症和化疗副作用中的相关性放在上下文中进行考虑。
