Lucia, UmbertoPonzetto, AntonioDeisboeck, Thomas2016-03-012016Lucia, Umberto, Antonio Ponzetto, and Thomas S. Deisboeck. 2016. “Constructal approach to cell membranes transport: Amending the ‘Norton-Simon’ hypothesis for cancer treatment.” Scientific Reports 6 (1): 19451. doi:10.1038/srep19451. http://dx.doi.org/10.1038/srep19451.2045-2322http://nrs.harvard.edu/urn-3:HUL.InstRepos:25658410To investigate biosystems, we propose a new thermodynamic concept that analyses ion, mass and energy flows across the cell membrane. This paradigm-shifting approach has a wide applicability to medically relevant topics including advancing cancer treatment. To support this claim, we revisit ‘Norton-Simon’ and evolving it from an already important anti-cancer hypothesis to a thermodynamic theorem in medicine. We confirm that an increase in proliferation and a reduction in apoptosis trigger a maximum of ATP consumption by the tumor cell. Moreover, we find that positive, membrane-crossing ions lead to a decrease in the energy used by the tumor, supporting the notion of their growth inhibitory effect while negative ions apparently increase the cancer’s consumption of energy hence reflecting a growth promoting impact. Our results not only represent a thermodynamic proof of the original Norton-Simon hypothesis but, more concretely, they also advance the clinically intriguing and experimentally testable, diagnostic hypothesis that observing an increase in negative ions inside a cell in vitro, and inside a diseased tissue in vivo, may indicate growth or recurrence of a tumor. We conclude with providing theoretical evidence that applying electromagnetic field therapy early on in the treatment cycle may maximize its anti-cancer efficacy.en-USJournal Article2016-03-0110.1038/srep19451