CLINICAL RESEARCH AND COMMERCIALIZATION FOR OUR CPRIT SUBMISSION.

Our suggestion of a CPRIT submission formulated on Oct 14th (see our posts) has excited our readers
we felt compelled to dig deeper in this story.  We basically suggested that in Prostate Cancer, the incidence was much higher as opposed to a relative low mortality.  We went on to say that this paradox begs scientists to find ways of discriminating which Prostate Cancer should be considered dangerous for our patient to compel us to aggressively treat the patient.  We suggested that a cancer that is spreading needs to be treated because only metastasis ( spread of the cancer) can kill the patient.  How to tell which cancer will spread?  We submitted that cancer cells before they spread, needed to lose their attachments to other cells by decreasing their Membrane Adhesion Molecules.  One of the Adhesion Molecule of interest was E-Cadherin.  We therefore suggested that in all cancers of the prostate, dosing the amount of Adhesion molecule was a way to predict its potential for spreading.  If we make it simple to quantify E-Cadherin, a kit can be commercialized to determine quickly the spread of disease.  We also suggested that cancer cells to penetrate tissues and leading to organ failure and killing the host, must create its road through cellular tissues.  It needs to secrete enzymes called Metalloproteases (2,9) to break through.  We suggested that a high level of these Metalloproteases in the biopsy tissue could predict a moving cancer.  A Kit to detect Metalloproteases could be commercialized to help Doctors take medical decisions for the benefit of patients.  All this, if proven in our intended research could advance medical practice.

There is further discussion to have about this:

1. Could Blocking Metalloprotease gene stop the spread of disease?
2. Could restoring E-Cadherin level or function stop the spread of disease?
Scientist from California believe that  activating P120 could restore E-Cadherin function efficiently enough to restore or correct deficiency of E-cadherin function.  Should we use this approach to slow down cancer.

The story of E-Cadherin is just beginning.  We know that cancer in fact spread very early.  In small cell lung cancers, Doctors perform a bone marrow biopsy to see that even in early stage, the cancer has already invaded away from the lung.  This is true also in Breast cancer where even in stage I (the first stage of Breast cancer) the Bone marrow could already be invaded.  The meaning of this distant invasion has been interpreted with controversy.  But even in these cases, it portend a bad prognosis.  Worse prognosis then that of patient with negative Bone Marrow finding. DOES E-CADHERIN REDUCTION CORRELATES WITH POSITIVE INVASION OF THE BONE MARROW?  COULD WE SPARE PATIENTS A BONE MARROW PROCEDURE IF THE E-CADHERIN IS LOW. These are some of the question that have a bearing on clinical matter and would impact today practice as we move forward.

The level of E-Cadherin has broad implications.  In Colon cancers, particularly in the Familial Adenomatous Polyposis (FAP), The E-cadherin level could predict not only evolution to cancer state of the Polyposis but also and again predict metastasis.  He even beg to suggest that it could have prognosis implication.  The decrease of E-cadherin has profound consequence on the amount the Beta-catenin that E-cadherin can not longer "sequester".   Whether this will lead to increase the Cyclin D level down the line could be assumed and therefore sustain life of cancer cell.  It is also worth mentioning that in the sequence of gene Mutation leading to Colorectal cancer, the loss of 5q (ADENOMA PHASE)which seems to correspond to the phase where Beta- Catenin is important is the earliest stage in the sequence of transformation.  This fact correspond to the "good Prognosis" of these cancer....COULD E-CADHERIN REDUCTION BE  AN EARLY SIGN OF COLORECTAL CANCER METASTASIS?  OR SHOULD THIS MODEL BE CHALLENGED?

Assuming we find a Molecule A which, when it is incorporated by the cell, it opens up and adopt a conformational change increasing phosphorylation of Beta-Catenin leading it to proteasomic destruction, could that decrease Cyclin D formation and induce Apoptosis?  What would be the impact if that incorporation was selective to cancer cells?  These are the challenges we face!

Through genetic intervention, could we restore the wnt-signalling pathways to prevent FAP and prevent removal of the Colon in FAP? Remember this, 80-85% of sporadic colorectal cancers have disturbance in the wnt pathways, what we are talking about could impact the majority of Colorectal cncers (second leading cause of cancer death in the United States)

Does the wide spread use of Calcium based product for Osteoporosis prevention correspond to decrease of Colorectal cancer in the terminal colon.  Calcium is critical in the function of membrane receptors.

The cure is achievable, let get it!