John Stamos - Public Service Announcement
Programmed Cell Death
After fifty years of experience with
cytotoxic drugs, why is there no widely accepted laboratory method to select chemotherapy for individual patients?
While there are many contributing factors, the medical research community's long fixation upon cell proliferation as the only valid endpoint for laboratory study has led to the development of assay methods which have failed (and continue to fail) to predict clinical outcomes for cancer patients. Tragically, these cumbersome and unreliable methods (i.e. Clonogenic, H3-Thymidine incorporation, etc.) have prejudiced oncologists against the entire field of assay-directed therapy and diverted attention away from a lifesaving technology.
The importance of the assay endpoint (cell death vs. cell growth)
Fortunately, new insights into the biology of human cancer have fostered a growing appreciation of the crucial role of programmed cell death, both apoptotic and non-apoptotic, in carcinogenesis.
The realization that cancer reflects a dysregulation of cell death demands that clinically relevant laboratory methods focus upon cytotoxicity, rather than upon growth inhibition. The most robust cell-death endpoint, delayed loss of membrane integrity (Cancer Research, Sept 15, 1993), which has been shown to correlate with response and survival in human cancer (J. Nat'l Canc.Inst., Oct 1991), serves as the principle underlying Rational Therapeutics™' EVA-PCD™ method. If we, in the clinical oncology community, are to realize the full potential that these techniques offer in the therapy of our patients, then we must be prepared to re-examine the field of primary culture assays in the newer context of cell death phenomena.
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