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)

The secret for Cure of cancer is located in the selective apoptosis, or cancer cell death

We know there are several ways that lead to cell death.  The main 2 ways are through the Extrinsic pathway which uses Receptors located at the skin of the cell called cellular membrane (receptors such as TNF-R1 and FAS) and Intrinsic pathways that use internal proteins (i.e. Caspases) that may destroy or paralyze  the breathing and energy producing organs of the cell called mitochondria. The challenge is to control these processes in the cell, know how to trigger them, and to do this only in the cancer cells without affecting the normal cells.  We need to know how to tag cancer cells, give that tag to a killing molecule that can attach to the apoptosis receptor.  This is just one way to be looking for a cure.  The complexity and multitude of metabolic pathways presents a problem, but also opportunities to kill the cancer cell.We are in the wee hours of learning them.Target therapy is in its early hour.

When there is a mistake in the gene during replication, there is a repair mechanism. To allow that repair,
the cell needs to be slowed down in its life cycle. This slowing seems to be the main action of P53. If repair does not occur, P53 leads the cell to cell destruction/apoptosis.  That's why most cancers remove or change the P53 to stay alive. Like most Molecules in the cell, the P53 has its own path to destruction. MDM2 seems to be that path to the loss of this so important P53.  Scientists are looking at knocking down MDM2 to see if this may restore the P53 function in those conditions where the P53 is not fundamentally altered.  We will follow this for you and give an update!

The Cure is achievable we know that for sure, we need just need to become better "cell mechanics"....stay tuned...