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Biooncology R-VEGF

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History of VEGF and angiogenesis research

Timeline of research milestones

A Tortuous Path: An Interactive Timeline; The history of VEGF and angiogenesis research is marked by a series of extraordinary scientific discoveries and innovations. The confluence of these seminal moments has created a growing body of knowledge. Genentech BioOncology has been, and continues to be, at the forefront of this exciting and expanding field of research.

Observation: A Hallmark Revealed; Late 1800s: Rudolf Virchow and other German pahtologists observe that some human tumors are highly vascularized.[1]

Observation: A Hallmark Revealed; 1927: Warren Lewis describes the tumor vasculature in rats, noting variations in vessel morphology among several different tumor types.[2]

Observation: A Hallmark Revealed; 1939: Using a tumor window model pioneered by J.C. Sandison, Gordon Ide and colleqgues observe a potent angiogenic response after implanting a tumor in a rabbit's ear and, thus, postulate the presence of tumor-derived vascular growth factors.[3]

Contemplation: A Question of Consequence; 1945: After correlating vessel count with tumor size, Glenn Algire and his team propose that neovascularization is an essential step in tumorigenesis.[4]

Contemplation: A Question of Consequence; 1968: By placing a filter between a tumor and host, Melvin Greenblatt and Phillipe Shubick, along with Robert Ehrmann and Mogens Knoth, test--and prove--the hypothesis that angiogenesis is induced by 1 or more diffusible, tumor-released growth factors.[5,6]

Inspiration: A New Quest Begins; 1971: In the first attempt to isolate a specific pro-angiogenic signal, Judah Folkman identifies a soluble 'tumor angiogenic factor' (TAF) that is 'mitogenic for endothelial cells and responsible for formatino of new capillaries.'[7]

Inspiration: A New Quest Begins; 1983: Separate gropus led by Donal Senger and Harold Dvorak identify and partially purify a protein shown to induce vascular leakage, na ming it vascular permeability factor (VPF).[8]

Inspiration: A New Quest Begins; 1989: Napoleone Ferrara and other Genentech researchers isolate and later clone a protein that is mitogenic only to endothelial cells. Because of this, they name the protein vascular endothelial growth factor (VEGF). Further tests reveal that VPF and VEGF are the same secreted protein.[9]

Inspiration: A New Quest Begins; 1992: In studies of glioblastoma multiforme, Eli Keshet and Karl Plate observe that VEGF expression is highest in the most ischemic sections fo hte tumor and postulate that hypoxia is a key environmental trigger of tumor angiogenesis.[10,11]

Inspiration: A New Quest Begins; 1992: Two tyrosine kinase VEGF receptors are identified--first VEGFR-1 (FLT1) by Carlie de Vries and colleagues and,later, VEGFR-2 (KDR) by a group led by Bruce Terman.[12,13]

Inspiration: A New Quest Begins; 1996: By demonstrating tha tknockou tof a single VEGF allele in mice resulted in embryonic lethality, Napoleone Ferrara and collaborators illustrate that VEGF is required for angiogenesis-assosicated normal embryonic development.[14]

Expectation: Where Will it Lead -- and Who Will Lead the Way? 2006: The search for understanding of angiogenesis and the role of VEGF in oncology continues. AS a key collaborator in many groundbreaking discoveries of the last 2 decades, Genentech BioOncology continues to lead the way in research on VEGF and it srole in teh development of multiple solid tumors, including lung, breast, and colorectal cancers. To learn mor eabout key Genentech contributors, click here.

References:
1.
Ferrara N. Nat Rev Cancer. 2002;2:795-803.
2.
Lewis WH. Bulletin of the Johns Hopkins Hospital. 1927;41:156-162.
3.
Ide AG, Baker NH, Warren SL. Am J Roentgenol. 1939;42:891-899.
4.
Algire GH, Chalkey HW, Legallis FY, Park HD. J Natl Cancer Inst. 1945;6:73-85.
5.
Greenblatt M, Shubik P. J Natl Cancer Inst. 1968;41:111-124.
6.
Ehrmann RL, Knoth M. J Natl Cancer Inst. 1968;41:1329-1341.
7.
Folkman J, Merler E, Abernathy C, Williams G. J Exp Med. 1971;133:275-288.
8.
Senger DR, Galli SJ, Dvorak AM, et al. Science. 1983;219:983-985.
9.
Ferrara N, Henzel WJ. Biochem Biophys Res Commun. 1989;161:851-858.
10.
Shweiki D, Itin A, Soffer D, Keshet E. Nature. 1992;359:843-845.
11.
Plate KH, Breier G, Weich HA, Risau W. Nature. 1992;359:845-848.
12.
Autiero M, Waltenberger J, Communi D, et al. Nat Med. 2003;9:936-943.
13.
Terman BI, Dougher-Vermazen M, Carrion ME, et al. Biochem Biophys Res Commun. 1992;187:1579-1586.
14.
Ferrara N, Carver-Moore K, Chen H, et al. Nature. 1996;380:439-442.