Capatina Alina L, Lagos Dimitris, Brackenbury William J
Department of Biology, University of York, York, UK.
Hull York Medical School, York, UK.
Rev Physiol Biochem Pharmacol. 2022;183:1-43. doi: 10.1007/112_2020_46.
Ion channels are key regulators of cancer cell pathophysiology. They contribute to a variety of processes such as maintenance of cellular osmolarity and membrane potential, motility (via interactions with the cytoskeleton), invasion, signal transduction, transcriptional activity and cell cycle progression, leading to tumour progression and metastasis. Ion channels thus represent promising targets for cancer therapy. Ion channels are attractive targets because many of them are expressed at the plasma membrane and a broad range of existing inhibitors are already in clinical use for other indications. However, many of the ion channels identified in cancer cells are also active in healthy normal cells, so there is a risk that certain blockers may have off-target effects on normal physiological function. This review describes recent research advances into ion channel inhibitors as anticancer therapeutics. A growing body of evidence suggests that a range of existing and novel Na, K, Ca and Cl channel inhibitors may be effective for suppressing cancer cell proliferation, migration and invasion, as well as enhancing apoptosis, leading to suppression of tumour growth and metastasis, either alone or in combination with standard-of-care therapies. The majority of evidence to date is based on preclinical in vitro and in vivo studies, although there are several examples of ion channel-targeting strategies now reaching early phase clinical trials. Given the strong links between ion channel function and regulation of tumour growth, metastasis and chemotherapy resistance, it is likely that further work in this area will facilitate the development of new therapeutic approaches which will reach the clinic in the future.
离子通道是癌细胞病理生理学的关键调节因子。它们参与多种过程，如维持细胞渗透压和膜电位、运动性（通过与细胞骨架相互作用）、侵袭、信号转导、转录活性和细胞周期进程，从而导致肿瘤进展和转移。因此，离子通道是癌症治疗的有前景的靶点。离子通道是有吸引力的靶点，因为它们中的许多在质膜上表达，并且大量现有的抑制剂已在临床上用于其他适应症。然而，在癌细胞中鉴定出的许多离子通道在健康的正常细胞中也有活性，因此存在某些阻滞剂可能对正常生理功能产生脱靶效应的风险。本综述描述了离子通道抑制剂作为抗癌治疗药物的最新研究进展。越来越多的证据表明，一系列现有的和新型的钠、钾、钙和氯通道抑制剂可能单独或与标准治疗方法联合有效地抑制癌细胞增殖、迁移和侵袭，以及增强细胞凋亡，从而抑制肿瘤生长和转移。尽管目前有几个针对离子通道的策略已进入早期临床试验阶段，但迄今为止的大多数证据基于临床前的体外和体内研究。鉴于离子通道功能与肿瘤生长、转移和化疗耐药性调节之间的紧密联系，该领域的进一步研究可能会促进新治疗方法的开发，并有望在未来进入临床应用。
