The electrical tumor microenvironment: abnormalities and opportunities

Abnormal electrical properties in cancerous tumors have been observed for more than a century. Modern technological advances have enabled rapid improvements in our understanding of these electrical facets and our ability to leverage this information for diagnosis and treatment. Here, we outline the current knowledge of the electrical tumor microenvironment (eTME), including electrical abnormalities at the tissue, cell, and molecular scales. Of particular interest to solid tumors and immunotherapy, the innate immune system responds profoundly to these abnormalities with altered mobility and effector function. Improved understanding of the eTME has enabled new advances in disease detection, with techniques such as impedance spectroscopy showing promise as minimally invasive, sensitive, and specific methods that complement traditional approaches. Therapeutic strategies that use electrical stimulation via externally applied fields, electrically active nanomaterials and devices, and so-called electroceuticals have shown promise in augmenting cancer therapy efficacy, particularly via leveraging the immune system. This review summarizes the state of the field, highlighting the eTME as a foundational - yet often overlooked - feature of cancer and a rapidly-growing area of novel therapeutic development.