Increased plasma vascular endothelial growth factor (VEGF) as a surrogate marker for optimal therapeutic dosing of VEGF receptor-2 monoclonal antibodies

Cancer Research
Guido BocciRobert S Kerbel

Abstract

A major obstacle compromising the successful application of many of the new targeted anticancer drugs, including angiogenesis inhibitors, is the empiricism associated with determining an effective biological/therapeutic dose because many of these drugs express optimum therapeutic activity below the maximum tolerated dose, if such a dose can be defined. Hence, surrogate markers are needed to help determine optimal dosing. Here we describe such a molecular marker, increased plasma levels of vascular endothelial growth factor (VEGF), in normal or tumor-bearing mice that received injections of an anti-VEGF receptor (VEGFR)-2 monoclonal antibody, such as DC101. Rapid increases of mouse VEGF (e.g., within 24 hours) up to 1 order of magnitude were observed after single injections of DC101 in non-tumor-bearing severe combined immunodeficient or nude mice; similar increases in human plasma VEGF were detected in human tumor-bearing mice. RAFL-1, another anti-VEGFR-2 antibody, also caused a significant increase in plasma VEGF. In contrast, increases in mouse VEGF levels were not seen when small molecule VEGFR-2 inhibitors were tested in normal mice. Most importantly, the increases in plasma VEGF were induced in a dose-dependent manner, wi...Continue Reading

References

Nov 18, 1971·The New England Journal of Medicine·J Folkman
Dec 1, 1995·The Journal of Clinical Investigation·J L WallaceG Cirino
Feb 20, 2002·FEBS Letters·Frode SelheimFlemming S Vassbotn
Mar 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jennifer TranRobert S Kerbel
May 23, 2002·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Antonella N WitmerReinier O Schlingemann
Jul 18, 2002·Nature Reviews. Drug Discovery·Massimo CristofanilliGabriel N Hortobagyi
Aug 13, 2002·Current Topics in Medicinal Chemistry·Stephen J Boyer
Aug 15, 2002·Proceedings of the National Academy of Sciences of the United States of America·Eugene S KimDarrell J Yamashiro
Oct 3, 2002·Nature Reviews. Cancer·Robert Kerbel, Judah Folkman
Oct 3, 2002·Nature Reviews. Cancer·Napoleone Ferrara
Nov 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Harold F Dvorak
Mar 7, 2003·American Journal of Physiology. Renal Physiology·Rebecca R FosterSteven J Harper
Aug 5, 2003·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Mogher KhamaisiAllan Flyvbjerg
Sep 27, 2003·Neoplasia : an International Journal for Oncology Research·Sophia RanPhilip E Thorpe
Jun 2, 2004·Nature Reviews. Cancer·Robert S Kerbel, Barton A Kamen
Jun 4, 2004·The New England Journal of Medicine·Herbert HurwitzFairooz Kabbinavar

❮ Previous
Next ❯

Citations

Mar 5, 2011·Cancer Chemotherapy and Pharmacology·Lakshmi RajdevJoseph A Sparano
Mar 11, 2008·Angiogenesis·Guo-Hua Fong
Oct 18, 2008·Angiogenesis·Arvind P PathakMichael S Pepper
Jun 15, 2011·Bioconjugate Chemistry·Hanmei XuZhendong Liu
Apr 6, 2011·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Steven I Sherman
Jan 13, 2006·Nature Clinical Practice. Oncology·Rakesh K JainJay S Loeffler
Jun 19, 2008·Nature Clinical Practice. Oncology·Cristiana SessaCurzio Rüegg
Jul 14, 2006·Nature Reviews. Cancer·Adrian M JubbHartmut Koeppen
Jul 25, 2008·Nature Reviews. Cancer·Gabriele Bergers, Douglas Hanahan
May 9, 2008·The New England Journal of Medicine·Robert S Kerbel
Aug 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Claire MeissirelPeter Carmeliet
Sep 13, 2006·Gut·J HeidemannT Kucharzik
Jun 3, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John F de GrootJohn V Heymach
Mar 26, 2013·OncoTargets and Therapy·Rajeev RajendraSeth M Pollack
Nov 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·John S RudgeGeorge D Yancopoulos
Oct 19, 2007·Proceedings of the National Academy of Sciences of the United States of America·John M L EbosRobert S Kerbel
Jul 23, 2014·Nature Reviews. Endocrinology·Yihai Cao
Oct 19, 2011·Journal of Oncology·Una AdamcicBrenda L Coomber
Mar 17, 2009·Expert Opinion on Pharmacotherapy·Annalisa Petrelli, Giorgio Valabrega
Apr 27, 2010·Expert Opinion on Investigational Drugs·Andre Cassell, Jennifer R Grandis
Jun 17, 2006·Cancer Investigation·Diana StempakSylvain Baruchel
Aug 15, 2014·Current Eye Research·Karolien HollandersIngeborg Stalmans
May 22, 2013·The Journal of Surgical Research·Leslie KnodJason S Frischer
Apr 13, 2011·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Eloisa Jantus-LewintreCarlos Camps
Jul 19, 2011·Cancer Treatment Reviews·Jordan Schmitt, Daniela Matei
Nov 28, 2009·Best Practice & Research. Clinical Endocrinology & Metabolism·Steven I Sherman
Nov 11, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Vanesa GregorcClaudio Bordignon
Apr 28, 2009·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Annamaria Rapisarda, Giovanni Melillo
May 29, 2007·Microvascular Research·Arindel S R Maharaj, Patricia A D'Amore
Apr 28, 2007·Trends in Molecular Medicine·Dan G DudaRakesh K Jain
Dec 25, 2008·Phytotherapy Research : PTR·Si-Jia HongSimon Ming-Yuen Lee

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.