CRAC通道在癌症中的作用:对治疗发展的影响。

IF 1 Q4 PHARMACOLOGY & PHARMACY Expert Review of Precision Medicine and Drug Development Pub Date : 2020-01-01 Epub Date: 2020-08-11 DOI:10.1080/23808993.2020.1803062
Husain Yar Khan, Iqra Mazahir, Shriya Reddy, Farzeen Fazili, AsfarSohail Azmi
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引用次数: 2

摘要

Ca2+释放激活的Ca2+ (CRAC)通道由Orai和STIM蛋白组成,是大多数不可兴奋细胞中Ca2+进入的主要途径之一。越来越多的证据表明,CRAC通道可以影响与肿瘤发生相关的各种过程。在几种类型的癌症组织和细胞中已经观察到CRAC通道蛋白的过表达,这表明阻断CRAC通道激活的Ca2+内流可以对癌症患者具有治疗益处。研究领域:本文主要研究了钙离子通道的分子组成和激活机制,以及钙离子通道在多种癌症中的作用。我们进一步描述了一些旨在开发CRAC通道阻滞剂的相关信息及其对癌症治疗的可能影响。为此,我们广泛地利用了PubMed上的可用文献。专家意见:靶向癌细胞中CRAC通道介导的Ca2+进入的可能性近年来引起了相当大的兴趣。与其他疾病相比,CRAC通道阻滞剂在癌症临床前研究和临床试验中的应用相对有限。未来在于开发和测试针对癌细胞特异性CRAC通道蛋白的更有效和选择性的药物,从而为癌症治疗开发开辟更好的途径。
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Roles of CRAC channel in cancer: implications for therapeutic development.

Introduction: The Ca2+release-activated Ca2+ (CRAC) channel, composed of Orai and STIM proteins, represents one of the main routes of Ca2+ entry in most non-excitable cells. There is accumulating evidence to suggest that CRAC channel can influence various processes associated with tumorigenesis. Overexpression of CRAC channel proteins has been observed in several types of cancer tissues and cells, indicating that blocking CRAC channel activated Ca2+ influx can have therapeutic benefits for cancer patients.

Areas covered: In this review, we have primarily focused on the molecular composition and activation mechanism of CRAC channel as well as the myriad roles this Ca2+ channel play in various cancers. We further describe relevant information about several efforts aimed at developing CRAC channel blockers and their likely implications for cancer therapy. We have extensively utilized the available literature on PubMed to this end.

Expert opinion: The possibility of targeting CRAC channel mediated Ca2+ entry in cancer cells has generated considerable interest in recent years. Use of CRAC channel blockers in cancer preclinical studies and clinical trials has been relatively limited as compared to other diseases. The future lies in developing and testing more potent and selective drugs that target cancer cell specific CRAC channel proteins, hence opening better avenues for cancer therapeutic development.

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来源期刊
CiteScore
2.30
自引率
0.00%
发文量
9
期刊介绍: Expert Review of Precision Medicine and Drug Development publishes primarily review articles covering the development and clinical application of medicine to be used in a personalized therapy setting; in addition, the journal also publishes original research and commentary-style articles. In an era where medicine is recognizing that a one-size-fits-all approach is not always appropriate, it has become necessary to identify patients responsive to treatments and treat patient populations using a tailored approach. Areas covered include: Development and application of drugs targeted to specific genotypes and populations, as well as advanced diagnostic technologies and significant biomarkers that aid in this. Clinical trials and case studies within personalized therapy and drug development. Screening, prediction and prevention of disease, prediction of adverse events, treatment monitoring, effects of metabolomics and microbiomics on treatment. Secondary population research, genome-wide association studies, disease–gene association studies, personal genome technologies. Ethical and cost–benefit issues, the impact to healthcare and business infrastructure, and regulatory issues.
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