Energy management- a critical role in cancer induction

cancer induction- age-associated; even very high-risk “cancer genes” such as BRCA-1 take many years to produce tumors, which suggests induction is a concatenated multi-factorial process. identifying cells that become at risk or pose the greatest clinical threat, “cancer stem-cells (CSC's) and Cancer Initiating Cells (CIC's)” are described as originators and metastatic initiators respectively. Energy discussed i.e. Intuitively, the hallmark of increased motility and invasiveness in cancer cells must require more ATP but paradoxically many cancer cells use glycolysis rather than oxidative phosphorylation (oxphos) to generate it (the Warburg effect)- related to the mitochrondria, changes in signalling; mitochondrial suppression through reactive oxygen species and hypoxia- responsive genes such as HIF; metabolic competition decided by proliferative state (the “Crabtree effect”). The energy used in cell interactions and motility of cell organelles is also important, in what the authors call Fractal Entropic self sorting. AMP kinase (AMPK) also upregualted in cancers, suggesting metabolic pathways maybe linked to AMPK and energy metabolism, together with fact the AMPK is linked to mTOR. Authors link IL-3 as a growth factor- i.e. withdrawing IL3 causes immediate cessation of glycolysis but has no effect on ATP levels. Authors propose a model- To summarise, the model predicts the following: 1. The degree of “malignant” activity is proportional to the degree of structural fluidity (simplification of entropic energy dissipation). 2. Cancer cells will exhibit mixed metabolism with a bias towards glycolysis. 3. Cancer cells will be poorly distinguished from the normal population, but “onco-antigens” may arise depending on how the degradation re-assembles protein complexes. 4. Many, and often multiple, mutations will arise but will be biased towards the phenotype of the originating cell; and they will take time to create an effect since these are stochastic and dependent on fractal connectivity, which is inherently stable. 5. Targeting specific mutations may, or may not, work depending on where that mutation sits in the fractal interfacing. The overall direction of energy dissipation in cells is from release of energy “locked in” in high-energy metabolic substrates (eg. sugars) into coherent and balanced structure and activity. During this process, energy is released and dissipated (entropy) -cancer is an imbalance in this energy re-distribution. Ref- Energy management- a critical role in cancer induction. Critical reviews in oncology.hematlology. 2013.