Treating cancer: is kill cure?

Abstract

For more than fifty years, the paradigm which has formed the basis of cancer research and treatment has been that of irreversibly deranged cells, which would inevitably kill their host unless they were totally eradicated. Experimentation procedures, evaluation criteria, and therapies are all based on cell killing. Yet there is substantial evidence that the kill/cure paradigm has reached its limit, and may be blinding us to other mechanisms to control this family of diseases. Both old and new data lead to the conclusion that the derangements in cellular function, while profound, are in large measure derivatives of normal mechanisms for organ growth, repair and renewal. Further, these are dynamic processes, potentially capable of reversal. If one views cancer as a community of cells in which signalling and communication is deranged, but functional, it becomes clear that cytotoxic approaches may serve to exacerbate the very control and communication defects which permit growth, invasion and metastasis. A new model is proposed, in which the cancer cell is seen as largely normal, but aberrantly regulated. Viewed from this perspective, the "cures" we have achieved may not be the result to total kill, but instead may result from a reassertion of control. This conceptualization offers an explanation for many laboratory and clinical observations, such as the induction of drug resistance medicated by pre-existing detoxification mechanisms, the cyclic progression of many tumours, and the compelling relationship between graft-versus-host disease and the long-term disease-free survival of transplanted leukaemia patients. Further, it opens conceptual avenues to new therapies and evaluation procedures.