Two separate bioelectricity studies have recently detailed an extremely sensitive cancer detection tool and a novel target for cancer immunotherapies. Both papers were published in Bioelectricity of Cancer, a special issue of the journal Bioelectricity, which will be available free of cost on their site until November 8.
In “Ultrasensitive System for Electrophysiology of Cancer Cell Populations: A Review”, authors Paulo Rocha, Aya Elghajiji, and David Tosh, of the University of Bath, U.K., detail the need for stronger technology to study cancer cells that yield very low levels of bioelectricity. The researchers created a bidirectional platform that records the electrical activity of cell populations over time. This allows researchers to observe the changes that occur in such cell cultures after adding different therapeutic agents.
This device contains a glass sensor with two parallel, circular gold electrodes, one serving as a measuring electrode and the other as a counter-electrode. These low impedance large area electrodes serve to minimize background noise in the system. The Bath team demonstrated their device’s ability to detect communication between cancer cells in both rat glioma cells and human prostate cancer cells. This technique brings researchers one step closer to the electrical detection, and potential treatment, of cancer. Being that this bioelectrical activity occurs early in the cancer progression, this would enable earlier detection and treatment of the disease. As for treatment, this bioelectric approach could eventually offer a non-toxic alternative to chemotherapy.
The second paper, “Extracellular K+ Dampens T-Cell Functions: Implications for Immune Suppression in the Tumor Microenvironment”, details the ion activity in the tumor microenvironment (TME). This paper was written by Navin Kumar Verma of the Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, with collaboration from the Agency for Science Technology and Research (Singapore), and the University of California, Davis.
The team found that a rise in the level of potassium ions (K+) in the TME caused by dying tumor cells could be used as a target for treatments that could enhance T-cell-based immunotherapy. This work showed that high uptake of K+ by lymphocytes significantly inhibited the proliferation of these anti-cancer cells and their cytokine production. In addition, it was also observed that this activity resulted in the up-regulation of immune checkpoint protein PD-1 expression.
With this knowledge, the team then screened a library of compounds to identify a novel activator (SKA-346) of a specific K+ channel in T-cells. The introduction of SKA-346 inhibited this suppressive effect of high K+ concentration on the T-cells. In a sense, this bioelectric occurrence involving K+ activity serves as a “secondary” checkpoint in cancer regulation.
Treatments like SKA-346 can be used in concert with PD-1 inhibitors and other drugs to further enhance patient outcomes. Being that immunotherapies often cause adverse side effects on cognition and other functions, it is best to use the lowest dose needed. This K+ channel modulator could potentially be used in concert with the traditional immunotherapies to lower their required dosages.
“These two articles, indeed all of the articles in this special issue, make evident the extraordinary power of looking at cancer from a bioelectrical perspective,” explained Dany Spencer Adams, Editor-in-Chief of Bioelectricity. “Bioelectricity is fundamental to life – no bioelectricity, no life. It should not be surprising that monitoring bioelectricity yields valuable information about a wide range of disease states. This issue demonstrates how monitoring that mis-regulation leads to valuable clues about why cancer cells behave so badly and what we can do about it. This collection also provides a template for how to look at other diseases. I am very grateful to Drs. Djamgoz and Arcangeli for this special issue.”
Bioelectricity’s promise for therapeutic targets in cancer – Two promising discoveries are well delineated: an ultra-sensitive tool to detect cancer and a new therapeutic target for cancer immunotherapy https://t.co/79I9DFqAVU
— Dr Neil Bodie (@neil_bodie) October 9, 2019