GKA deel 1 college 14

Angiogenesis inhibitors Folkman Sci Am 275-3, 1996 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],GK 2009 Drug Possible mechanism of action Current status CAI Inhibits Ca²+ influx, suppresses endothelial cells Phases I and II CM101 Induces inflammation in tumors, destroying growing capillaries Phase I Interferon  Decreases FGF production (made by tumor cells) Phase II Interleukin-1,2 Increases production of angiogenic inhibitor Phase I Marimastat Inhibits enzymes that destroy ECM Phases II and III Thalidomide Unknown? Phases I and II TNP-470 Inhibits proliferation endothelial cells Phases I and II Platelet factor 4 Inhibits proliferation endothelial cells Phases I and II Pentosan polysulfate Blocks effect of growth factors on endothelial cells Phases I

Angiogenesis inhibitors Folkman Sci Am 275-3, 1996 ,[object Object],[object Object],[object Object],[object Object],GK 2009 VEGF FGF

Surgery of primary tumor allows metastasis to grow Folkman Sci Am 275-3, 1996 ,[object Object],[object Object],[object Object],GK 2009 =============== http://angiogenesis.amgen.com/

From bench top to bedside Barinaga, Science 278, 1997, 1036-1039 ,[object Object],[object Object],GK 2009

From bench top to bedside Barinaga, Science 278, 1997, 1036-1039 ,[object Object],[object Object],GK 2009 Herceptine ONYX-015 Gleevec Farnesyl

Fatty anchor of Ras Barinaga, Science 278, 1997, 1036-1039 ,[object Object],[object Object],[object Object],[object Object],[object Object],GK 2009

Effect van ONYX-015 Barinaga, Science 278, 1997, 1036-1039 GK 2009 The ‘adeno-trick’: Ellisen en Haber

Cancer drug: Gleevec=Glivec=imatinib=STI-571 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],GK 2009

Gleevec ,[object Object],[object Object],[object Object],[object Object],GK 2009 ============== Becker, Nature Biotechnol 2004, 22, 15-18 ,[object Object]

Targeting Tyrosine Kinases in Cancer: The Second Wave Jose Baselga, Science 2006, 312, 1175-1178 ,[object Object],[object Object],GK 2009 ===============

The hallmarks of cancer Hanahan & Weinberg, Cell 100, 2000, 57-70 GK 2009

The hallmarks of cancer Hanahan & Weinberg, Cell 100, 2000, 57-70 GK 2009 Mantovani Nature 457, 36-37(2009)

GKA deel 1 college 14

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