Wednesday, January 9, 2013

FOR THE CURE, TIME FOR PARADIGM SHIFT AND A REVOLUTION AGAINST SOME OF OUR LEADERS IN CANCER MEDICINE

Cancer is a disease involving the cell.  Our current understanding is that during the course of our lives, somewhere in our system, a cell's function will be altered enough to transform a normal cell into A CANCER CELL.   Our current understanding is that all cells want to stay alive and for cancer cell multiplication and dissemination it appears to be assurance of a type of cell preservation.  We know that to survive, the cancer cell will escape several mechanisms.  How to stimulate its growth, how to escape detection by the immune system and removal by the Macrophages and related natural measures, how to stay awake by lighting up certain pathways, how to resist against external chemical attacks, how to repair damages caused by attacks, how to survive on their own etc.?

We also know that cancer cells are not the same not only by tissue of origin, but also by pathways driving them.  We know that to escape death, the cancer cell uses redundancies and loopholes in its pathways, that is it may alter or multiply these pathways to overrun incoming inhibitions.  It may amplify measures to block our reach toward programmed death.  The cancer cell knows that once programmed death mechanisms are started, it has to die.  It builds things like Bcl-2 around the Caspase death path.  The cancer cell knows that there are inhibitory forces that need to be altered.  P53 is one of the Major forces. It needs to be altered or mutated.  Flow through a pathway is another force. And altering regulators may be one way to control the flow.  Or leaving a switch on to drive the pathways. etc...

We also know that every major target in pathways has effects downstream toward the nucleus and its DNA, and upstream toward the Membrane.  For some, we have found lateral connections serving as loophole escape.  More than one phenotype of an important Target is meant to provide Resistance to attacks of the main type.
 
With chemotherapy, we have had some success.  Our failures reside in the mechanisms of resistance, in the ability of the cancer cell to repair itself and escape death.  Escaping death appears to be also solely linked to protection against Necrosis and programmed death.

We also know about Driver pathways as well as forces we can use to stop cell migration, division and seeding. We have got to use this knowledge to plan our action for the cure.

The success of target therapy needs to tell us that leaders who continue to push chemotherapy as the only alternative, creating more combinations, need to be more and more left alone, while we switch to Targeting therapy and some combination therapies.

Targeting therapy tells us we got to get better at defining Driver pathways to be effective.  Particularly in solid tumors.  This is the major priority.  HOW DO YOU TELL THIS IS A DRIVER TARGET OR PATHWAY? IS IT BY DOSING REGULATORY MOLECULES, ENZYMES ALONG A PATHWAY, LEVEL OF TRANSCRIPTION GENES, STATUS OF SWITCH TO TARGET MOLECULES, PROMOTER EXPRESSION?  HOW DO YOU SAY THIS IS THE DRIVER PATHWAY?  WITH THIS KNOWLEDGE WE CAN AVOID STUDIES LIKE TAXOTERE & REVLIMID IN PROSTATE CANCER, WHEN TAXOTERE & VELCADE WOULD HAVE BEEN BETTER.

IF WE KNOW HOW TO DO THIS, OUR PATH TO CURE IS ASSURED.

The second question: HOW TO GET THIS CELL TO CASPASE, TO LYSOZOMAL HYDROLASES AND CATHEPSINS, AND OTHER NECROTIC AND AUTOPHAGIC PROCESSES? HOW TO PUSH IT TO PROGRAMMED DEATH?

TIME TO WAKE UP AND SMELL THE COFFEE BEFORE ANOTHER RUN FOR THE CURE! 

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