Thermodynamics and Electro-Biologic Prospects for Therapies to Intervene in Cancer Progression

Joseph      Molnar; Barry   S.   Thornton; Elysia      Thornton-Benko; Leonard      Amaral; Zsuzsanna      Schelz; Mihaly      Novak

Abstract

The second law of thermodynamics does not allow us to make entropy barriers, but it does not exclude changing the direction of some particular components of entropy flow from a tumour to the normal tissues. The reversal of entropy flow in co-existing normal and tumour tissues may halt tumour development due to reversed signal transmission in the tumour-host entity. This thermodynamic approach may help in the design of cancer therapy. Different pathways are involved in the de-regulation of cell proliferation leading to cancer. Although many signalling and genomic approaches have been successfully identified, a variety of other processes are associated with carcinogenesis, some of which have been established for the therapy of solid cancers. The topic of survival of individual patients is related to some thermodynamic and other features of the cancer. For example, therapeutic prospects can be improved when based on the needs and opportunities of traditional therapies and thermodynamic interventions by considering the irregular or discontinuous growth of tumours. To explain basic differences between metabolism of normal and cancer cells the first and second laws of thermodynamics are applied together with changes in the electrical properties of the cell membrane and cell interior. Thermodynamic features of tumour organisation are maintained by entropy production and exchange. The differences in basic factors of entropy production between normal and cancer cells determine the direction of fluxes and consequently can be targets of specific interventions in cancer therapy. The basic routes of entropy production are: availability of mobile electrons, electrical polarization and depolarization, membrane potentials, ion fluxes, pH, temperature, chemical and electric potential, Gibbs energy, nutrition, chemotactic constraints, growth kinetics, mobilization of nutrients (proteins, fatty acids), dielectric differences, conductivity and response rate to external forces. Any one or a combination of these may be considered as possible new targets for selective modification of tumour growth. Differences in electro physiological, thermodynamic and metabolic activities of normal and cancer cells are compared and discussed in this review including some current research. New therapeutic strategies are now receiving support from many biomedical fields which we hope will contribute to successful therapy of solid cancers.

Keywords: First and second law of thermodynamics applied to tumor growth-host relationship, entropy, negentropy, charge transfer, factors controlling membrane based fluxes, competition between cancer and normal cells, potential targeting of factors that determine rate and direction of tumor growth, therapeutic opportunities