Thursday, May 16, 2013

EMBRACE THE CHANGES OR DIE

With the progress in genetics, the field of Oncology is bound to change.  The volume of work done in the field of genetics as it relates to oncology, has moved this field from what it was, a research area, to center stage daily Oncology practice.  Knowledge of CHOP and combination Etoposide -Cisplatin or even Taxol-Carboplatin indications, is shrinking in importance in the Ipilimumab and Crizotinib world.  The thing is as we getting closer to actually cure cancer we have understood that knowing more about natural chemical pathways in the cell, and treating cancer based on this knowledge has yielded better results in response rates and disease free progression and sometimes in overall survival.  This evidence has convinced most Oncologists that it is time to move to the Target therapy movement and brace our selves for the new "TARGETOLOGY" IN MEDICAL ONCOLOGY.
TARGETOLOGY IS NOT JUST THE STUDY OF CELLULAR TARGETS, it is the full command of treatments that address the law of Nature.
- Genes controlling DNA, DNA repair, DNA stability, and mechanisms therewith to maintain the integrity of the Nuclear Material and its Epigenetic environment.
-  Genes involved in key the Cellular pathways and corollary pathways
- Genes of proliferation
- Genes of cellular metabolism amplification and regulator genes
- Genes of differentiation (Mesangial and endodermal transformation vs epithelialization)
- Genes of Cellular Adaptation
- Genes of electrical conduction and hidden pathways (Wnt, Notch)
- Genes controlling cellular adaptation
- Genes driving Metastasis, transport and membrane vacuole formation
- Genes  of Receptors and cellular Adhesion
We should stress that the mechanisms used by the cell to impose the direction of Homeostasis based on flight or stay needs, response to environment stimuli, and sense of purpose imposed by the notch and cell differentiation.  The notion of Core Binding Factor should be extended to all protein complexes imposing cellular Metabolism direction as it is evident that that's how the cell operates!
The notion that some Cancers use specific drivers that can be somewhat is easily identified (CML) vs cancers that are using regulator enzymes (certain Leukemias) or epigenic events, should be brought forth.
Some proliferative disorders find their driver effect in shifts in gene Methylation or splicing patterns rather than actually in changing or mutating genes.  But clearly, most cancers come from a failure of receptors with subsequent increase of growth factors which end up imposing growth and Mutations in unwanted areas!  Among the unrecognized mechanisms is deficiency of location of important effector proteins.  In other words, failure in transport. Traffic has to go on from Membranes to Nucleus, transport failure for one reason or another, failure of vacuolization that allows exocytosis, function of Golgi apparatus and  lysozome. Do not forget the Ribosome and Mitochondria!  Some of the organelles are so important that they have their own genome!
The point is that it is time to now be reacquainted with cell biology to be an efficient Oncologist because that is where the answer is!  Avoiding this fact will not cut it!  It is the way to the future! Manipulating chemical destruction by using standard chemotherapy has failed to give more cures!  We have met drug resistance and the power of cell adaptatio. It is past time to rethink our strategies and Targetology is here now and to stay!

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