Springer Targeting Notch in Cancer: From the Fruit Fly to the Clinic

The serendipitously discovered link between developmental biology and cancer, touched of an explosion of discoveries on the role of Notch in human malignancies, including every aspect of cancer biology, from control of differentiation, proliferation and apoptosis in transformed cells to angiogenesis, tumor-stroma interaction and anti-cancer immune responses. A number of observations have revealed that Notch even plays a role in the renewal of cancer stem cells and tumor initiating cells, which are thought to be a major cause of resistance to treatment. Targeting Notch in Cancer will provide researchers, oncologists, pharmacologists and students with a detailed understanding of the intricate cross-talk between Notch and other pathways of therapeutic interest so to better design rational drug combinations for specific diseases and disease subsets. Divided into two parts, Part I describes in detail what we know about the genetics, molecular biology, biochemistry and structural biology of Notch, as well as the role of Notch in such processes as angiogenesis and immune surveillance. Without insights gained from these basic studies, rational targeting of Notch in human disease would be impossible. Part II describes the role of Notch and ongoing experimental therapeutic efforts in the most important subtypes of human cancers, organized in a clinically oriented fashion by organs and systems affected From the Back Cover The serendipitously discovered link between developmental biology and cancer, touched of an explosion of discoveries on the role of Notch in human malignancies, including every aspect of cancer biology, from control of differentiation, proliferation and apoptosis in transformed cells to angiogenesis, tumor-stroma interaction and anti-cancer immune responses. A number of observations have revealed that Notch even plays a role in the renewal of cancer stem cells and tumor initiating cells, which are thought to be a major cause of resistance to treatment. Targeting Notch in Cancer will provide researchers, oncologists, pharmacologists and students with a detailed understanding of the intricate cross-talk between Notch and other pathways of therapeutic interest so to better design rational drug combinations for specific diseases and disease subsets. Divided into two parts, Part I describes in detail what we know about the genetics, molecular biology, biochemistry and structural biology of Notch, as well as the role of Notch in such processes as angiogenesis and immune surveillance. Without insights gained from these basic studies, rational targeting of Notch in human disease would be impossible. Part II describes the role of Notch and ongoing experimental therapeutic efforts in the most important subtypes of human cancers, organized in a clinically oriented fashion by organs and systems affected About the Author Dr. Miele is the Cancer Crusaders Professor of Cancer Research and Chair of the Department of Genetics, School of Medicine, at the Louisiana State University Health Sciences Center, New Orleans, Louisiana. Dr. Miele completed his M.D. and Ph.D. degrees summa cum laude at the University of Naples, Italy, in 1982 and 1987 respectively. His Ph.D. dissertation work was conducted at the Max-Planck Institute for Molecular Genetics, Berlin, Germany. After a postdoctoral fellowship and at the National Institutes of Health in the Human Genetics Branch, Section on Developmental Genetics, Dr. Miele started his independent research career in 1993 at the Center for Biologics Evaluation and Research, U.S. Food and Drug Administration. There, he took on a project on the then recently discovered human NOTCH gene. His research has been focused on Notch signaling in cancer for the past 25 years, with a mechanistic and translational emphasis. In 1998, Dr. Miele moved to Loyola University's Cardinal Bernardin Cancer Center, where he discovered the anti-apoptotic activity of Notch1 in le