Chinese a Nti鄄 Cancer a Ssociation

The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology. The members of the family, VEGF-A (also known as VEGF), VEGF-B, VEGF-C, VEGF-D, and placenta growth factor (PIGF), play important roles in vascular biology in both normal physiology and pathology. The generation of a humanized neutralizing antibody to VEGF-A (bevacizumab, also known as Avastin) and the demonstration of its benefit in numerous human cancers have confirmed the merit of an anti-angiogenesis approach to cancer treatment and have validated the VEGF-A signaling pathway as a therapeutic target. Other members of the VEGF family are now being targeted, and their relevance to human cancer and the development of resistance to anti-VEGF-A treatment are being evaluated in the clinic. Here, we discuss the potential of targeting VEGF family members in the diagnosis and treatment of cancer.

[1]  S. Stacker,et al.  Proteolytic processing of vascular endothelial growth factor‐D is essential for its capacity to promote the growth and spread of cancer , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[2]  G. Viglietto,et al.  Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[3]  K. Alitalo,et al.  Proprotein convertases promote processing of VEGF‐D, a critical step for binding the angiogenic receptor VEGFR‐2 , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[4]  Masahiro Inoue,et al.  Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. , 2009, Cancer cell.

[5]  P. Hewett,et al.  Vascular endothelial growth factor-D expression is an independent prognostic marker for survival in colorectal carcinoma. , 2002, Cancer research.

[6]  G. Mann,et al.  Targeting lymphangiogenesis to prevent tumour metastasis , 2006, British Journal of Cancer.

[7]  P. Rothwell,et al.  Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials , 2011, The Lancet.

[8]  P D Scotney,et al.  Human vascular endothelial growth factor B: Characterization of recombinant isoforms and generation of neutralizing monoclonal antibodies , 2002, Clinical and experimental pharmacology & physiology.

[9]  M. Skobe,et al.  Complete and specific inhibition of adult lymphatic regeneration by a novel VEGFR-3 neutralizing antibody. , 2005, Journal of the National Cancer Institute.

[10]  Napoleone Ferrara,et al.  VEGF and the quest for tumour angiogenesis factors , 2002, Nature Reviews Cancer.

[11]  I. Kasman,et al.  Anti‐VEGF antibody therapy does not promote metastasis in genetically engineered mouse tumour models , 2012, The Journal of pathology.

[12]  Y. Hirata,et al.  Molecular cloning of a novel vascular endothelial growth factor, VEGF-D. , 1997, Genomics.

[13]  S. Stacker,et al.  Molecular Control of Lymphatic Metastasis , 2008, Annals of the New York Academy of Sciences.

[14]  S. Stacker,et al.  Lymphangiogenic growth factors as markers of tumor metastasis , 2004, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[15]  W. You,et al.  VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer. , 2011, Cancer research.

[16]  F. Becker,et al.  Growth and metastasis of tumor in organ culture , 1963, Cancer.

[17]  K. Alitalo,et al.  Suppressive Effects of Vascular Endothelial Growth Factor-B on Tumor Growth in a Mouse Model of Pancreatic Neuroendocrine Tumorigenesis , 2010, PloS one.

[18]  S. Stacker,et al.  The VD1 neutralizing antibody to vascular endothelial growth factor-D: binding epitope and relationship to receptor binding. , 2011, Journal of molecular biology.

[19]  J. Pollard,et al.  VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling , 2011, Nature Cell Biology.

[20]  J. Desai,et al.  Towards the biomarker-guided rational use of antiangiogenic agents in the treatment of metastatic colorectal cancer , 2012 .

[21]  Yihai Cao,et al.  Proteolytic processing regulates receptor specificity and activity of VEGF‐C , 1997, The EMBO journal.

[22]  E C Nice,et al.  Monoclonal antibodies to vascular endothelial growth factor-D block its interactions with both VEGF receptor-2 and VEGF receptor-3. , 2000, European journal of biochemistry.

[23]  R. Moritz,et al.  Plasmin Activates the Lymphangiogenic Growth Factors VEGF-C and VEGF-D , 2003, The Journal of experimental medicine.

[24]  Thomas Hawighorst,et al.  Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis , 2001, Nature Medicine.

[25]  T. Veikkola,et al.  Distinct roles of vascular endothelial growth factor-D in lymphangiogenesis and metastasis. , 2007, The American journal of pathology.

[26]  Thijs J. Hagenbeek,et al.  PlGF Blockade Does Not Inhibit Angiogenesis during Primary Tumor Growth , 2010, Cell.

[27]  Christian Fischer,et al.  FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy? , 2008, Nature Reviews Cancer.

[28]  M. Piccart-Gebhart,et al.  Bevacizumab and Breast Cancer: A Meta-Analysis of First-Line Phase III Studies and a Critical Reappraisal of Available Evidence , 2012, Journal of oncology.

[29]  John M L Ebos,et al.  Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. , 2009, Cancer cell.

[30]  F. Peale,et al.  Differential drug class‐specific metastatic effects following treatment with a panel of angiogenesis inhibitors , 2012, The Journal of pathology.

[31]  K. Alitalo,et al.  Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[32]  S. Koch,et al.  Signal transduction by vascular endothelial growth factor receptors. , 2012, Cold Spring Harbor perspectives in medicine.

[33]  L. Orci,et al.  Vascular endothelial growth factor‐C‐mediated lymphangiogenesis promotes tumour metastasis , 2001, The EMBO journal.

[34]  W. Hendrickson,et al.  A structural superfamily of growth factors containing a cystine knot motif , 1993, Cell.

[35]  S. Stone-Elander,et al.  Vascular endothelial growth factor B controls endothelial fatty acid uptake , 2010, Nature.

[36]  K. Alitalo,et al.  Lymphatic Vessels as Targets of Tumor Therapy? , 2001, The Journal of experimental medicine.

[37]  Tara Karnezis,et al.  VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium. , 2012, Cancer cell.

[38]  Bing Li,et al.  Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo , 1993, Nature.

[39]  K. Alitalo,et al.  Genomic Organization of the Mouse and Human Genes for Vascular Endothelial Growth Factor B (VEGF-B) and Characterization of a Second Splice Isoform* , 1996, The Journal of Biological Chemistry.

[40]  M. Giacca,et al.  Anti-PlGF Inhibits Growth of VEGF(R)-Inhibitor-Resistant Tumors without Affecting Healthy Vessels , 2007, Cell.

[41]  Ichiro Mori,et al.  Prognostic significance of vascular endothelial growth factor D in breast carcinoma with long-term follow-up. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[42]  M. Kanda,et al.  Correlations of the expression of vascular endothelial growth factor B and its isoforms in hepatocellular carcinoma with clinico‐pathological parameters , 2008, Journal of surgical oncology.

[43]  J. Folkman.  Tumor angiogenesis: therapeutic implications. , 1971, The New England journal of medicine.

[44]  D. Goeddel,et al.  Vascular endothelial growth factor is a secreted angiogenic mitogen. , 1989, Science.

[45]  S. Stacker,et al.  Localization of vascular endothelial growth factor‐D in malignant melanoma suggests a role in tumour angiogenesis , 2001, The Journal of pathology.

[46]  K. Alitalo,et al.  Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling. , 2002, Journal of the National Cancer Institute.

[47]  S. Stacker,et al.  VEGF-D is an X-linked/AP-1 Regulated Putative Onco-angiogen in Human Glioblastoma Multiforme , 2001, Molecular medicine.

[48]  R. Moritz,et al.  Biosynthesis of Vascular Endothelial Growth Factor-D Involves Proteolytic Processing Which Generates Non-covalent Homodimers* , 1999, The Journal of Biological Chemistry.

[49]  A. Palotie,et al.  Novel human vascular endothelial growth factor genes VEGF-B and VEGF-C localize to chromosomes 11q13 and 4q34, respectively. , 1996, Circulation.

[50]  D. Yee.  Faculty Opinions recommendation of Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. , 2009 .

[51]  L. Qin,et al.  Opportunities and challenges in tumor angiogenesis research: back and forth between bench and bed. , 2012, Advances in cancer research.

[52]  D. Connolly,et al.  Vascular permeability factor, an endothelial cell mitogen related to PDGF. , 1989, Science.

[53]  H. W. Chalkley,et al.  Vasculae Reactions of Normal and Malignant Tissues in Vivo. I. Vascular Reactions of Mice to Wounds and to Normal and Neoplastic Transplants , 1945 .

[54]  M. Shibuya,et al.  Expression of a functional VEGFR-1 in tumor cells is a major determinant of anti-PlGF antibodies efficacy , 2011, Proceedings of the National Academy of Sciences.

[55]  P. Rothwell,et al.  Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials , 2012, The Lancet.

[56]  J. Berlin,et al.  Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. , 2004, The New England journal of medicine.

[57]  M. Giacca,et al.  Further Pharmacological and Genetic Evidence for the Efficacy of PlGF Inhibition in Cancer and Eye Disease , 2010, Cell.

[58]  S. Oliviero,et al.  Identification of a c-fos-induced gene that is related to the platelet-derived growth factor/vascular endothelial growth factor family. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[59]  T. Veikkola,et al.  Signalling via vascular endothelial growth factor receptor‐3 is sufficient for lymphangiogenesis in transgenic mice , 2001, The EMBO journal.

[60]  K. Alitalo,et al.  A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. , 1996, The EMBO journal.

[61]  Steven A. Stacker,et al.  VEGF-D promotes the metastatic spread of tumor cells via the lymphatics , 2001, Nature Medicine.

[62]  D. Ribatti.  Novel angiogenesis inhibitors: addressing the issue of redundancy in the angiogenic signaling pathway. , 2011, Cancer treatment reviews.

[63]  R. Goldberg,et al.  TREATMENT OF METASTATIC COLORECTAL CANCER Review of recent advances , 2005 .

[64]  D. Hicklin,et al.  Review: Monoclonal Antibodies to the Vascular Endothelial Growth Factor Receptor-2 in Cancer Therapy , 2007, Clinical Cancer Research.

[65]  Kenneth J. Hillan,et al.  Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer , 2004, Nature Reviews Drug Discovery.