Phillips Jade A, Hutchings Charlotte, Djamgoz Mustafa B A
Department of Life Sciences, Imperial College London, London, United Kingdom.
Biotechnology Research Center, Cyprus International University, Nicosia, North Cyprus.
Bioelectricity. 2021 Mar 1;3(1):14-26. doi: 10.1089/bioe.2020.0051. Epub 2021 Mar 16.
We support the notion that the neural connections of the tumor microenvironment (TME) and the associated 'bioelectricity' play significant role in the pathophysiology of cancer. In several cancers, the nerve input promotes the cancer process. While straightforward surgical denervation of tumors, therefore, could improve prognosis, resulting side effects of such a procedure would be unpredictable and irreversible. On the other hand, tumor innervation can be manipulated effectively for therapeutic purposes by alternative novel approaches broadly termed "electroceuticals." In this perspective, we evaluate the clinical potential of targeting the TME first through manipulation of the nerve input itself and second by application of electric fields directly to the tumor. The former encompasses several different biophysical and biochemical approaches. These include implantable devices, nanoparticles, and electroactive polymers, as well as optogenetics and chemogenetics. As regard bioelectrical manipulation of the tumor itself, the "tumor-treating field" technique, applied to gliomas commonly in combination with chemotherapy, is evaluated. Also, as electroceuticals, drugs acting on ion channels and neurotransmitter receptors are highlighted for completeness. It is concluded, first, that electroceuticals comprise a broad range of biomedical tools. Second, such electroceuticals present significant clinical potential for exploiting the neural component of the TME as a strategy against cancer. Finally, the inherent bioelectric characteristics of tumors themselves are also amenable to complementary approaches. Collectively, these represent an evolving, dynamic field and further progress and applications can be expected to follow both conceptually and technically.
我们支持这样一种观点，即肿瘤微环境（TME）的神经连接以及相关的“生物电”在癌症的病理生理学中发挥着重要作用。在几种癌症中，神经输入会促进癌症进程。因此，虽然直接对肿瘤进行手术去神经支配可能会改善预后，但这种手术产生的副作用将是不可预测且不可逆转的。另一方面，可以通过统称为“电治疗药物”的替代新方法有效地操纵肿瘤神经支配以达到治疗目的。从这个角度出发，我们首先评估通过操纵神经输入本身，其次通过直接向肿瘤施加电场来靶向TME的临床潜力。前者包括几种不同的生物物理和生化方法。这些方法包括可植入装置、纳米颗粒和电活性聚合物，以及光遗传学和化学遗传学。关于对肿瘤本身的生物电操纵，我们评估了通常与化疗联合应用于神经胶质瘤的“肿瘤治疗电场”技术。此外，作为电治疗药物，为全面起见，还重点介绍了作用于离子通道和神经递质受体的药物。得出的结论是，首先，电治疗药物包括广泛的生物医学工具。其次，这类电治疗药物在利用TME的神经成分作为抗癌策略方面具有显著的临床潜力。最后，肿瘤本身固有的生物电特性也适用于互补方法。总的来说，这些代表了一个不断发展的动态领域，预计在概念和技术上都将取得进一步进展和应用。
