Summary While a genetic basis for cancer is well established, the mechanism(s) by which it is induced remain obscure. Paradoxically, although the spectrum of oncogenic mutations is extremely wide, all cancer cells universally exhibit a characteristic profile regardless of origin, whose progression is extremely predictable: increased proliferation, invasion and migration, loss in architectural integrity (anaplasticity), apoptotic inactivation etc. To understand this discrepancy, an extensive review was performed from the standpoint that since all oncogenes directly or indirectly alter enzyme pathways which control energy management, this may be a critical component of the induction process; alterations in management divert energy away from the construction and maintenance of stable complex structure into dynamic activity such as continuing replication, motility and migration, and architectural fluidity, ie. anaplasticity. This diversion would flow from the laws of thermodynamics which require energy to be dissipated (entropy). The review prompted a model (Fractal Entropy) whereby cellular entropic dissipation follows structure-independent fractal distributions rather than the linearly ordered, sequential pathways currently modelled for signal transduction. ¡°Malignant¡± behaviour arises from disturbances which bias this fractal network to achieve maximum entropy. Because replication, motility and architectural plasticity all actively dissipate more energy through kinetic activity than by structure-building in which energy becomes ¡°locked in¡±, these routes are preferred eventually generating a universal malignant phenotype independent of the types of mutations and pathways initially affected. A proposed mechanism for the model is based on Chaos and Fractal theories illustrated in the Appendix. These present examples of dynamic fractal behaviour through Mandelbrot figures and of how Chaos theory can initiate and guide distribution of entropy fractals.
This proposal accords fully with established physical laws and the most recent research, and reconciles many of the unresolved problems concerning genetic heterogeneity, the universality of malignant cell behaviour, cancer progression, and the well-known, but still unexplained, metabolic Warburg effect. An established in vitro cell model offers evidence for the hypothesis which suggests new directions for multi-disciplinary research into the origin of cancer.
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