Monday, December 17, 2012

STRATEGIES FOR THE CURE

Since the work of Weinberg and Hanahan, we know that despite the varieties of cancer, 6 driving forces lead to cancer cell survival.  The "Hallmarks of cancer" result from:

1.Self sufficiency in growth signals: Cancer cells escape Anoikis,  They secrete their own growth factors to achieve an autocrine stimulation.

2.Insensitivity to anti-growth signals. This is achieved by changing membranes' receptors composition and number, boosting its own global growth, and secreting Tumor Necrosis factors to tamper with surrounding cell machinery.

3.Sustained Angiogenesis, to maintain "feeding" of the new tumor mass.  This is mostly critical for solid tumors.  It is critical in tumors that bleed easily such as renal cell cancers.

4.Limitless replicative potential.  By removing stops to mass formation, natural boundary sensors which contribute to shaping organs, Telomerase activation again.

5. Suppressing or escaping Apoptosis: By using cyclins and Bcl-2 and related molecules. Shielding Mitochondria and avoiding FAS/BAX, activating loopholes routes and impairing ubiquitination of growth molecules!

6.Tissue invasion and metastasis. Here the tumor cells alter composition, nature and amount of the cell receptors and adhsions molecules, cluster of differentiation (CD), and produce Tumor growth factors (TGF) which give it growth advantage vis-a-vis the surrounding tissue.

This list is by no mean exhaustive given the variety of possible oncogene mutations.  However, when one gene is causing one of the 6 pathways, it is dubbed a DRIVER mutation for that cancer, and may have significant therapeutic importance.

This 6 venues are made of important molecular structures that can be a Target for therapy. Researcher are combing them one by one and targeting them.  The successful experience with Multikinase therapy suggest that interrupting several points of the cascade appears beneficial.  Computer models are being developed to see if sequential attacks or coordinated combinations would be better models for future therapies.  The CRBCM is working to develop such a model. Our model will be complete after we enumerate all laws of nature (see our related series).

Model of cures should embrace these 6 venues in a mathematical equation...the challenge is launched!
 
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