Department of Life Sciences, Imperial College London, London, UK.
Biotechnology Research Centre, Cyprus International University, Nicosia, Mersin, Turkey.
Rev Physiol Biochem Pharmacol. 2022;183:251-277. doi: 10.1007/112_2021_66.
Ion transporting proteins (ITPs) comprise a wide range of ion channels, exchangers, pumps and ionotropic receptors many of which are expressed in tumours and contribute dynamically to the different components and stages of the complex cancer process, from initiation to metastasis. In this promising major field of biomedical research, several candidate ITPs have emerged as clinically viable. Here, we consider a series of general issues concerning the oncological potential of ITPs focusing on voltage-gated sodium channels as a 'case study'. First, we outline some key properties of 'cancer' as a whole. These include epigenetics, stemness, metastasis, heterogeneity, neuronal characteristics and bioelectricity. Cancer specificity of ITP expression is evaluated in relation to tissue restriction, splice variance, functional specificity and macro-molecular complexing. As regards clinical potential, diagnostics is covered with emphasis on enabling early detection. For therapeutics, we deal with molecular approaches, drug repurposing and combinations. Importantly, we emphasise the need for carefully designed clinical trials. We highlight also the area of 'social responsibility' and the need to involve the public (cancer patients and healthy individuals) in the work of cancer research professionals as well as clinicians. In advising patients how best to manage cancer, and live with it, we offer the following four principles: Awareness and prevention, early detection, specialist, integrated care, and psychological support. Finally, we highlight four key prerequisites for commercialisation of ITP-based technologies against cancer. We conclude that ITPs offer significant potential as regards both understanding the intricacies of the complex process of cancer and for developing much needed novel therapies.
离子转运蛋白 (ITPs) 包括广泛的离子通道、交换器、泵和离子型受体，其中许多在肿瘤中表达，并动态地参与肿瘤发生的不同组成部分和阶段，从起始到转移。在这个有前途的生物医学研究主要领域中，已经出现了几种有临床应用前景的候选 ITP。在这里，我们考虑了与 ITP 的肿瘤潜力有关的一系列一般问题，重点关注电压门控钠离子通道作为“案例研究”。首先，我们概述了“癌症”作为一个整体的一些关键特性。这些特性包括表观遗传学、干性、转移、异质性、神经元特性和生物电学。我们评估了 ITP 表达的癌症特异性与组织限制、剪接变异、功能特异性和大分子复合物形成的关系。就临床潜力而言，诊断学是重点，强调早期检测。至于治疗学，我们处理分子方法、药物再利用和组合。重要的是，我们强调需要精心设计临床试验。我们还强调了“社会责任”领域的必要性，需要让癌症研究专业人员和临床医生参与癌症患者和健康个体的工作。在为癌症患者提供如何最好地管理和应对癌症的建议时，我们提出了以下四个原则：意识和预防、早期检测、专科、综合护理和心理支持。最后，我们强调了基于 ITP 的癌症治疗技术商业化的四个关键前提条件。我们得出结论，ITPs 在理解癌症这一复杂过程的复杂性以及开发急需的新型疗法方面具有重要的潜力。
