Importance of Hypoxia in cancer Biology

Hypoxia is not unexpected in normal cellular biology and mechanism to deal with are well set even at gene level.  The existence of Hypoxia induced Factor gene is a proof of the such a process.  Its interaction with the Von Hippel Lindau gene well described as it induce the clear cell kidney cancer.  hypoxia result in increased free Radicals and various acids (hypochloric, acetic acids, superoxide, and Hydrogen peroxide).

local conditions may worsen the toxic conditions of these highly "Reactive Oxygen Species" (ROS).  In certain tissues or condition  where there is highly "catalytic Iron or Cupper" (liver or substancia Nigra) the hypoxia (or Alcohol) will yield highly toxic molecules that will "burn" local tissues.  In a attempt to remedy the situation, the body will engage angiogenic genes to bring about new blood vessel to improve the local Oxygen levels.  (VEGF, and subsequently the EGFR will be highly engaged).  In the lungs, there is a typical cancer that happens in non smokers that has high expression of mutations of the EGFR, and respond highly to Gefitinib and Tarceva.  Checking for EGFR Mutation is now standard of care in lung cancer, meaning failure to evaluate EGFR is careless care since there is a unique response of these cancers that should be used prior to considering other therapies!
The Anoxic process happens in the Cytoplasm and the peri-nuclear region popularly knwon these day as epigenetic Zone.  It also involve where the cell breath or the Mitochondria.   With the involvement of the Mitochondria comes the MTOR.  Because the MTOR are here downstream from the EGFR, combination of Anti-EGFR with the MTOR inhibitor failed to show addititive effects in some cancers.  It is now suggested that the MTOR inhibitors follow the anti-EGFR as if the early use of anti-EGFRs prepare the way to the effect (somewhat sensitize) of the MTOR inhibitors.  Further proof of concept is needed although suggestions have been put forth.

The body has mechanisms to dampen the effects of the above toxic agents of which production has been boosted by the wide inconsiderate use of Anti-Oxidants (ignorance of potential presence of highly catalytic iron and Cupper, or Zinc for that matter).  We know what ionized Aluminum does for Parkinson disease...
Glutathion, Nicotinamid Adenine Dinucleotide (NAD), Nerf2, and other dismutase and various Sirtuins are our mechanisms of control.

The report suggesting the almighty Bcl-2 uses depletion of Gluthatione to block Apoptosis from ensuing point to the importance of Gluthatione in biologic events!

(TO BE CONTINUED)