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Ultra-sensitive tool to detect cancer and new therapeutic target for immunotherapy discovered

Two promising discoveries have been published in a special issue which features in the journal Bioelectricity

These include an an ultra-sensitive tool to detect cancer and a new therapeutic target for cancer immunotherapy. 

In the article entitled "Ultrasensitive System for Electrophysiology of Cancer Cell Populations: A Review" coauthors Paulo Rocha, Aya Elghajiji, and David Tosh, University of Bath, U.K., describe the need for more sensitive electrophysiology tools to study cancer cell populations that typically produce very low levels of bioelectricity.

Rocha et al. designed an ultra-sensitive bidirectional platform that allows electrical recordings of cell populations over time, making it possible to measure changes that occur with the addition of pharmacological compounds.

The system comprises a glass sensor on which are mounted two parallel, circular gold electrodes, one acting as the measuring electrode, the other as the counter-electrode.

Background noise is minimised by combining these low impedance large area electrodes.

The authors demonstrate the use of this system by detecting cancer cell-cell communication in rat glioma cells and in human prostate cancer cells.

This new approach brings electrical detection (and treatment) of cancer closer.

This is an exciting prospect since such bioelectric signals occur very early in the cancer process and bioelectric therapies would be expected to be "non-toxic" unlike, say, chemotherapy.

Also of interest is another article titled: "Extracellular K Dampens T-Cell Functions: Implications for Immune Suppression in the Tumour Microenvironment." 

This paper is concerned with ionic events in the tumour microenvironment (TME).

The researchers show that a rise in the level of potassium ions (K ) in TME, due to release from dying tumour cells, could be exploited as a valuable therapeutic target that could boost the effectiveness of T-cell-based immunotherapy.

This study demonstrated that the high K , taken up by the anti-tumour T-cells (lymphocytes), significantly inhibited their proliferation as well as their production of cytokines whilst up-regulating the expression of the immune checkpoint protein PD-1.

The authors then screened a library of compounds and identified a novel activator of a particular K channel (activated by calcium) in T-cells.

Application of this activator (SKA-346) rescued the T-cells from the suppressive effect of the high level of K in TME.

Thus, this bioelectric phenomenon identified a "secondary" checkpoint in cancer.

Accordingly, compounds like SKA-346 can be used alongside known PD-1 inhibitors and other cancer therapeutics to improve treatment and patient outcomes.

Immunotherapy frequently suffers from side effects, including adverse effects on cognitive function, so reducing its dosage by synergising it with ion channel modulators would be welcome.

"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," said 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," added Adams.

Source: Mary Ann Liebert INC / Genetic Engineering News



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