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CA Cancer J Clin 2007; 57:225-241
doi: 10.3322/canjclin.57.4.225
© 2007 American Cancer Society
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 The Lethal Phenotype of Cancer: The Molecular Basis of Death Due to Malignancy
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The Lethal Phenotype of Cancer

The Molecular Basis of Death Due to Malignancy

Robert D. Loberg, PhD, Deborah A. Bradley, MD, Scott A. Tomlins, Arul M. Chinnaiyan, MD, PhD and Kenneth J. Pienta, MD

Dr. Loberg is Research Assistant Professor, Internal Medicine and Urology, University of Michigan, Ann Arbor, MI.
Dr. Bradley is Fellow, Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI.
Mr. Tomlins is Graduate Student, Department of Pathology, University of Michigan, Ann Arbor, MI.
Dr. Chinnaiyan is S. P. Hicks Endowed Professorship; Professor of Pathology and Urology; Director of Pathology Research Informatics; and Director of Cancer Bioinformatics, University of Michigan, Ann Arbor, MI.
Dr. Pienta is Professor, Internal Medicine and Urology; and American Cancer Society Clinical Research Professor, University of Michigan, Ann Arbor, MI.

This article is available online at http://CAonline.AmCancerSoc.org
To earn free CME credit for successfully completing the online quiz based on this article, go to http://CME.AmCancerSoc.org
Disclosures: K.J.P. is supported by an American Cancer Society Clinical Research Professorship. A.M.C. is supported by a Burroughs Welcome Foundation Award in Clinical Translational Research. S.A.T. is supported by the Medical Scientist Training Program and a Rackham Predoctoral Award. This research was supported in part by National Institutes of Health Grant RO1 CA102872 (to K.J.P.); RO1 CA97063 (to A.M.C.); U01 CA111275 (to A.M.C.); P50 CA69568 (to K.J.P., A.M.C.); Department of Defense Grant PC051081 (to A.M.C.); Ralph Wilson Medical Research Foundation Award (K.J.P.); and a Prostate Cancer Foundation Research Award (R.D.L.)

The last decade has seen an explosion in knowledge of the molecular basis and treatment of cancer. The molecular events that define the lethal phenotype of various cancers—the genetic and cellular alterations that lead to a cancer with a poor or incurable prognosis—are being defined. While these studies describe the cellular events of the lethal phenotype of cancer in detail, how these events result in the common clinical syndromes that kill the majority of cancer patients is not well understood. It is clear that the central step that makes most cancers incurable is metastasis. Understanding the traits that a cancer acquires to successfully grow and metastasize to distant sites gives insight into how tumors produce multiple factors that result in multiple different clinical syndromes that are lethal for the patient.






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