(肿瘤生物学)Hallmarks of CancerThe Next Generation ().pdf

Leading Edge Review Hallmarks of Cancer: The Next Generation Douglas Hanahan1,2,* and Robert A. Weinberg3,* 1The Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, EPFL, Lausanne CH-1015, Switzerland 2The Department of Biochemistry Biophysics, UCSF, San Francisco, CA 94158, USA 3Whitehead Institute for Biomedical Research, Ludwig/MIT Center for Molecular Oncology, and MIT Department of Biology, Cambridge, MA 02142, USA *Correspondence: dh@epfl.ch (D.H.), weinberg@ (R.A.W.) DOI 10.1016/j.cell.2011.02.013 The hallmarks of cancer comprise six biological capabilities acquired during the multistep develop- ment of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and acti- vating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hall- mark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list—reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hall- mark traits by creating the ‘‘tumor microenvironment.’’ Recognition of the widespread applicability of these concepts will increasingly af