MAPPING CANCER AND CLUSTERS OF DIFFERENTIATION

MAPPING CANCER AND CLUSTERS OF DIFFERENTIATION.

One important aspect of the fight for the cure is to obtain cancer distribution MAP in an individual.  Certainly, one would not attack an enemy without knowing its size, quantity/quality, distribution and location.  One of the challenges with cancer is that it comes from normal cells, therefore any attack we plan should include a component regarding how to avoid hurting the normal cell which relies on same survival strategies and components as the cancer cell!  Luckily, the cancer cell wants to avoid many of the natural death processes.  It wants to migrate and invade other organs, and where it has newly invaded, it wants to grow faster than the local cells and therefore creates a nutrition supply system that favors it!   With each of the new needs the cancer wants to acquire, it has to develop new sets of molecules and mechanisms not necessarily expressed by the normal cell.  These are globally called CLUSTERS OF DIFFERENTIATION OR CD. These include changes in membrane receptors, driver mutations, status of activation of now known targets in various pathways, and of course changes in transcription factors, DNA and even chromatin conformations.

These clusters of differentiation have been divided according to not only how we could use them, but how the cancer cell uses them.  We call them Predictive as they can help us predict the existence and behavior of cancer.  They are Prognostic when they determine cancer resilience  to a given treatment and define or influence the outcome of the patient.  They are Diagnostic when they point to the existence of cancer (these include the so called "Tumor Markers").

Mapping cancer today is limited.  Staging cancer today is a crude way of mapping the extent of cancer.  But in this day and age when we can visualize radiological changes in the metabolism, knowing the exact location and number of cancer cells everywhere in our body, it appears to be an achievable goal.  The cure will not be secured until we can count remaining enemies.  This knowledge will also help define cure.  There is a perception in the treating physician community that cure is not Zero cancer cells.  That we could be "cured" despite a residual amount of cancer.  How much and where is not clear!  Those who believe in a threshold number of cancer cells for active disease assert that, under the threshold, the immune system keeps things under control.
Molecular Therapy attacking Clusters of Differentiation have been attached to chemotherapy drugs and to radiation particles to kill exclusively cancers cells that have them.  Campath, Rituxan and others follow these mechanisms.  Suffice is to say we need more sophisticated ways to MAP CANCER IN OUR BODIES!  THIS WILL BE THE STRONGEST DIAGNOSTIC, PREDICTOR AND DETECTOR OF CANCERS!

 MERRY CHRISTMAS / JOYEUX NOEL TO ALL!

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!