title: An integrated multidisciplinary model describing initiation of cancer and the Warburg hypothesis.
abstract: BACKGROUND
  In this paper we propose a chemical physics mechanism for the initiation of the glycolytic switch commonly known as the Warburg hypothesis, whereby glycolytic activity terminating in lactate continues even in well-oxygenated cells. We show that this may result in cancer via mitotic failure, recasting the current conception of the Warburg effect as a metabolic dysregulation consequent to cancer, to a biophysical defect that may contribute to cancer initiation.
  
  
  METHODS
  Our model is based on analogs of thermodynamic concepts that tie non-equilibrium fluid dynamics ultimately to metabolic imbalance, disrupted microtubule dynamics, and finally, genomic instability, from which cancers can arise. Specifically, we discuss how an analog of non-equilibrium Rayleigh-Benard convection can result in glycolytic oscillations and cause a cell to become locked into a higher-entropy state characteristic of cancer.
  
  
  CONCLUSIONS
  A quantitative model is presented that attributes the well-known Warburg effect to a biophysical mechanism driven by a convective disturbance in the cell. Contrary to current understanding, this effect may precipitate cancer development, rather than follow from it, providing new insights into carcinogenesis, cancer treatment, and prevention.
authors.affiliation: Center of Cancer Systems Biology, GeneSys Research Institute, Tufts University School of Medicine, Boston, MA 02142, USA. edward.rietman@tufts.edu
authors.forename: Edward A
authors.initials: EA
authors.lastname: Rietman
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Friesen
authors.forename: Philip
authors.initials: P
authors.lastname: Hahnfeldt
authors.forename: Robert
authors.initials: R
authors.lastname: Gatenby
authors.forename: Lynn
authors.initials: L
authors.lastname: Hlatky
authors.forename: Jack A
authors.initials: JA
authors.lastname: Tuszynski
mesh_terms: D002471:Cell Transformation, Neoplastic; D003599:Cytoskeleton / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D008962:Models, Theoretical; D009369:Neoplasms / Q000473:pathology*; D015388:Organelles / Q000378:metabolism; D013816:Thermodynamics