Skelding Kathryn A, Barry Daniel L, Theron Danielle Z, Lincz Lisa F
Cancer Cell Biology Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, New South Wales 2308, Australia.
Hunter Medical Research Institute, New Lambton Heights, New South Wales 2305, Australia.
Explor Target Antitumor Ther. 2022;3(1):62-89. doi: 10.37349/etat.2022.00072. Epub 2022 Feb 28.
The importance of Ca signaling, and particularly Ca channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions of TPC2 and a discussion of its potential as a target for therapeutic intervention, including a summary of clinical trials examining the TPC2 inhibitors, naringenin, tetrandrine, and verapamil for the treatment of various cancers is provided.
钙信号传导,尤其是钙通道,在癌细胞功能的关键事件(如增殖、转移、自噬和血管生成)中的重要性,最近才开始受到重视。特别值得注意的是双孔通道(TPCs),这是一组最近发现的位于内溶酶体系统中的钙通道。TPC2最近已成为具有重要病理生理相关性的细胞内离子通道,特别是在癌症方面,并且人们已经开始探索其作为抗癌药物靶点的作用。本文提供了TPC2与癌症相关功能的概述,并讨论了其作为治疗干预靶点的潜力,包括对研究TPC2抑制剂(柚皮素、粉防己碱和维拉帕米)治疗各种癌症的临床试验的总结。