Energy management – a critical role in cancer induction?

• Published in: Critical reviews in oncology/hematology 2013-10, Vol.88 (1), p.198-217
• Main Author: Garland, J
• Format: Article
• Language: English
• Subjects: Anaplasticity; Cancer; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Chaos; Energy management; Energy Metabolism; Entropy; Fractal; Hematology, Oncology and Palliative Medicine; Humans; IL3; Metabolism; Models, Biological; Mutation; Neoplasms - etiology; Neoplasms - metabolism; Review; Warburg effect
• ISSN: 1040-8428; 1879-0461
• DOI: 10.1016/j.critrevonc.2013.04.001

Abstract The variety of genes implicated in cancer induction is extensive but paradoxically all cancer cells behave in an identical and highly predictable fashion. This behaviour is closely correlated with a group of cellular morphological criteria termed Anaplasticity which involves increases/changes in: motility; invasion; replication; nuclear and chromosomal fragmentation; structural degradation; and phenotypic fluidity. Anaplasticity is so predictive it is a universal clinical yardstick for assessment and treatment. To understand this paradox, perceived mechanisms of cancer induction are reviewed and a new proposal made, namely that cancer is a diversion of energy required for structural organisation into maximum energy dissipation (entropy) through increased dynamic activities. This process is driven by oncogenic mutations or a variety of other permanent molecular alterations which re-direct “channels” distributing energy dissipation. These are organised along fractal networks (Fractal Entropy) and are not necessarily structure-dependent. “Oncogenic” alterations of any kind create cumulative effects by permanently stabilising parts of the fractal network, resulting in fractured co-ordination and re-direction of entropy into increased dynamic activity, which is the universal hallmark of cancer. The mechanism of Fractal Entropy employs Chaos and Fractal theories and is illustrated with Mandelbrot figures for fractal distributions and Chaos theory for its influence in creating fractal distributions and their behaviours. The proposal is examined in an in vitro heamatopoietic model (IL3 dependent cells) concerning regulation by growth factors of metabolism, apoptosis, oncogenesis and cell dormancy, and suggests new avenues of multi-disciplinary research. 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 m