THIRD LAW OF NATURE, NO PROLIFERATION AND CONCURRENT DIFFERENTIATION. HOW THIS LAW CAN BE USED FOR CANCER CURE

While the first and second law refer to the well being of the nucleus for protection of the cell division and its integrity, the 3rd law pertain to cell differentiation.  Basically the first law say that if DNA is altered, cell need to be stopped to allow correction.  And the powerful P53 Activation has been put in place for that.   Significant alteration of DNA will send powerful signal to P53, cause itS activation, and lead to cell cycle arrest.  This is where the power of Cisplatin based combinations reside.  And sure enough, this the basis of the notion that strong repair system will weaken this type of drug.  The all notion of Microsatellite Instability and its role in cancer is based on this law.

The 2nd law, is significant destruction of the scaffold of Mitosis, the Microtuble and all actinic or actinic like molecules which makes mitosis impossible should lead to cell destruction no matter what.  The intergrity of this system of Microtubule and filament not only control the critical phases of Mitosis (Metaphase, Anaphase), it control the integrity of membrane but also the cytoskeleton and cell mobility.  It is the nervous system of the cell and the control of various anchors.  Organelles of the cell are not just free flowing in general, they are anchored  to the Reticulum membrane most of the time (unless destined to Autophagia for cell preservation) and important Molecules involved in Apoptosis such as Cytochrome are attached to Mitochondrial membranes.   Suffice is to say that major alteration to these line of proteins will bypass major Cytosol based protection including the Bcl-2.  This is the strenghth  base of Taxol and Ixabepilone.  It is the explanation for neuropathy and cardiac toxicity of Adriamycin. It is partially the explanation of Q-T prolongation etc.

The 3rd law is more complex, cell differentiation should not go with full proliferation.  Cell that are fully differentiated should not be multiplying like crazy. and for sure, we do not want hundred  of livers, 3 brain or 99 lungs.  Have wonder why Atypia goes along with cancer transformation.  Well you have to lose differentiation to restart multiplying again!  And the poorly differentiated, the worse the magnitude of cancer.
The story of differentiation goes like this:

All cells have the same genome.  But based on their position, internal and external stimuli, they will  go one way or the other to specialize in a certain function for tissue and organ specialty.  The external stimuli could be a change of Oxygen content, Ph, or messages from your neighbor cells sending growth messages etc.  Internal stimuli are cytokines, morphogens, growth factors and signaling molecules or intracellular particulates.  These will stimulate Receptors or pathways (such as the NF-kB) and cause genetic and epigenetic consequences in the Nucleus.  Expression of genes which the cell want and need to be specialized will be achieved through heavy duty transcription of genes.  On the other hand, to control the uniqueness of the tissue, epigenetic closure of  multiplying capability genes is first completed to seal the deal on the fate of the cell.  Differentiation is like an EXIT door.   you can enter, but don't try coming back.  And once you enter, immediately you are taking care by the transcription machinery directing you to where you should be going and you lose multiplication ability.   The door however is not fully irreversibly closed.  In cancer the flow of force reverse and instead of moving forward, the door is reopen and the differentiation machinery is reversed or disabled (poor differentiation), the door is reopen, and the cell start to multiply again as part of the cancerous process.   Studies of Estrogen effect Vs Progesterone has shed some light in this case.  When one look at estrogen, it has more effect on the Exit door, constantly pushing that door toward Multiplication than Progesterone that has little effect of the door but with similar effect on the terminal differentiation.  Making Estrogen more cancer inducing than progesterone.  Yes taking Estrogen gives you the relief of symptoms but it is the push toward reversing the Exit door flow (toward proliferation transcription) that is the problem!
Is expression of H3K or FG2 the markers of Exit door tinkering, we are working hard to determine this.

AS ONE LOOK AT THIS FLOW TOWARD DIFFERENTIATION, A SLEW OF THERAPEUTIC TARGETS  EMERGE, THE ARRAY GOES FROM :

1. NEIGHBOR MESSAGES
2. ENVIRONMENT CHANGES
3. BLOCKING RECEPTOR UPSTREAM THE NF-kB AND COMPARABLE PATHWAYS
4. BLOCKING  THE PATHWAYS
5. SEALING THE DOOR
6. METHYLATION OF GENES, AND PARALYZING OR MODULATING ENZYMES INVOLVED IN EPIGENETIC CHANGES (PCAF, p300 MAY BE)
7. BLOCKING TRANSCRIPTION MACHINERY, EXPRESSION OR GENES DIRECTLY.

CERTAINLY, SIGNS OF RESUMPTION IN ACTIVITY OF GENES MEANT FOR PROLIFERATION IS AN EARLY SIGN OF CANCEROUS TRANSFORMATION, AND The BEST WAY TO DETERMINE THAT A DRUG IS CANCER PRODUCING.

AS A MATTER OF FACT, THIS IS HOW PAMIDRONATE AND OTHER BIPHOSPHONATE ACT TO CONTROL CANCER, BY INCREASING DIFFERENTIATION AND RELIEVING PRESSURE ON THE EXIT DOOR.

WELL DIFFERENTIATED TUMORS WILL HAVE A BETTER PROGNOSIS BECAUSE THEIR GENERAL FLOW OF FORCE IS STILL TOWARD DIFFERENTIATION AND NOT THROUGH THE PROLIFERATION DOOR .

WE ARE WORKING HARD AT CRBCM!