TAILIEUCHUNG - The Hallmarks of Cancer

It is important to note that the metastatic cells do not float about in isolation; rather, they reside within the extra-cellular matrix (ECM) of the host organ. The ECM is a complex mesh of proteins that fill voids be- tween cells, and it participates in the development of both healthy and cancer cells through chemical and mechanical signalling. There is evidence that changes in the stiffness of the ECM affect the signalling and hence the progress of the cancer. In turn, it seems that the cancer cells can interact with the ECM to trigger the very physical changes that favour the tumour’s development. Thus, in effect, metastatic cells create a “nest”. | Cell Vol. 100 57-70 January 7 2000 Copyright 2000 by Cell Press The Hallmarks of Cancer Review Douglas Hanahan and Robert A. Weinbergt Department of Biochemistry and Biophysics and Hormone Research Institute University of California at San Francisco San Francisco California 94143 t Whitehead Institute for Biomedical Research and Department of Biology Massachusetts Institute of Technology Cambridge Massachusetts 02142 After a quarter century of rapid advances cancer research has generated a rich and complex body of knowledge revealing cancer to be a disease involving dynamic changes in the genome. The foundation has been set in the discovery of mutations that produce oncogenes with dominant gain of function and tumor suppressor genes with recessive loss of function both classes of cancer genes have been identified through their alteration in human and animal cancer cells and by their elicitation of cancer phenotypes in experimental models Bishop and Weinberg 1996 . Some would argue that the search for the origin and treatment of this disease will continue over the next quarter century in much the same manner as it has in the recent past by adding further layers of complexity to a scientific literature that is already complex almost beyond measure. But we anticipate otherwise those researching the cancer problem will be practicing a dramatically different type of science than we have experienced over the past 25 years. Surely much of this change will be apparent at the technical level. But ultimately the more fundamental change will be conceptual. We foresee cancer research developing into a logical science where the complexities of the disease described in the laboratory and clinic will become understandable in terms of a small number of underlying principles. Some of these principles are even now in the midst of being codified. We discuss one set of them in the present essay rules that govern the transformation of normal human cells into malignant cancers. We .

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