Showing posts with label anti-proliferative. Show all posts
Showing posts with label anti-proliferative. Show all posts

Thursday, October 10, 2013

IT IS ALL ABOUT THE CYTOKINES!

The discovery of DNA and nuclear material has led to the emphasis on the alteration of Nuclear functions to fight cancer, indeed most of the original chemotherapy drugs had mechanisms of action centered on breaking or somehow impairing DNA.  This focus to a certain extent affected our judgement in the evaluation of certain drugs.  We are now finding out that the strength of certain drug  (and weakness /susceptibility to resistance) is not really due to their main effect on DNA (ie. epigenetic disturbances induced by  Etoposide).  The discovery that BCL-2 has a mechanism of resistance to certain drugs is point in case that nuclear material induced disturbances have significant limitations that occur away from the nucleus (at the Mitochondria).  Anti-proliferative chemotherapies have now shown their limits and scientists have kept this in our panoply of options against cancer.

Scientists have long been fascinated by the laws of nature, these driving forces that drive in certain ways or directions the chains of chemical reactions within the cells.  From Glycogenolysis to the Krebs' cycle, to the cellular pathways, role of enzymes these catalysts of chemical reaction and gene regulators, our focus has been progressively shifting.   The maximal effect of standard chemotherapy having been realized, the shift now has gone to driver Mutations, blocking pathways and modulating reactions etc.   But beyond the mutation, gene alterations and so forth, one thing that make a cancer spread like a wild fire is its stimulation by a growth factor, or its self dependence in achieving survival most of the time at very different levels of energy expenditure!  This role squarely falls into the area of epigenetics which is the critical area of Cytokine production determination.  Now, once produced, Cytokines, to be effective, must connect to their receptors!  This is where the wheels rub the asphalt to speed up the chemical reactions!

One of the mechanisms of increased cytokine production, aside from their gene amplification, is failure at the receptor.  Indeed, when a receptor fails, the normal reaction (law of nature) is to concur the resistance by sending more of the same cytokine.  While this increase could be partially succesful in restoring homeostasis depending on the level of abnormality at the receptor, the relative increase has other side effects due to the non specificity of receptors.  Co-receptors or other receptors susceptible to the same cytokine find themselves super excited and are driving downstream reactions at higher rates.  A SIGNIFICANT PHENOMENON NEEDS TO OCCUR AT THIS POINT, THAT IS THE DESENSITIZATION OF SECONDARY RECEPTORS, A TRAUMATIC PHENOMENON WITH POTENTIALLY NEOPLASTIC CONSEQUENCES   (TO BE CONTINUED)