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Bioelectrical approaches to cancer as a problem of the scaling of the cellular self

Journal

PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
Volume 165, Issue -, Pages 102-113

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbiomolbio.2021.04.007

Keywords

Ion channel; Gap junctions; Evolution; Multicellularity; Morphogenesis; Regeneration

Funding

  1. Barton Family Foundation
  2. Science Research 2.0.

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Understanding cancer through the lens of developmental biology reveals it as a consequence of breakdown in cell communication, leading to morphogenetic disorders. Bioelectric signaling plays a crucial role in coordinating morphogenetic processes, with modulation of bioelectric states showing potential in preventing or normalizing tumors. The harnessing of bioelectrically-mediated information flows represents a promising avenue in cancer research.
One lens with which to understand the complex phenomenon of cancer is that of developmental biology. Cancer is the inevitable consequence of a breakdown of the communication that enables individual cells to join into computational networks that work towards large-scale, morphogenetic goals instead of more primitive, unicellular objectives. This perspective suggests that cancer may be a physiological disorder, not necessarily due to problems with the genetically-specified protein hardware. One aspect of morphogenetic coordination is bioelectric signaling, and indeed an abnormal bioelectric signature non-invasively reveals the site of incipient tumors in amphibian models. Functionally, a disruption of resting potential states triggers metastatic melanoma phenotypes in embryos with no genetic defects or carcinogen exposure. Conversely, optogenetic or molecular-biological modulation of bioelectric states can override powerful oncogenic mutations and prevent or normalize tumors. The bioelectrically-mediated information flows that harness cells toward body-level anatomical outcomes represent a very attractive and tractable endogenous control system, which is being targeted by emerging ap-proaches to cancer. (c) 2021 Elsevier Ltd. All rights reserved.

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