Abstract
No clinically effective chemoprevention for lung cancer has been found. Angiogenesis is an early feature of both adenocarcinoma and squamous cell lung cancer. We investigated the effects of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2) inhibition on lung carcinogenesis in a murine model of adenocarcinoma. The VEGFR-2 tyrosine kinase inhibitor, vandetanib, was given to FVB/N mice in chow for 7 days at varying doses to show pharmacologic activity by inhibition of VEGF-mediated VEFGR-2 and ERK phosphorylation. Plasma levels corroborated adequate dosage. For chemoprevention experiments, mice were injected i.p. with 1 mg/g of urethane, a carcinogen found in tobacco smoke. Chow containing vandetanib, 75 mg/kg/d, or control chow was given to mice, starting 7 days after urethane administration. Sixteen weeks after urethane injection, mice were sacrificed, tumors enumerated and measured. Vandetanib resulted in reductions in tumor multiplicity (6.5 +/- 0.86 versus 1.0 +/- 0.30, P = 0.001) and average tumor volume (0.85 +/- 0.10 versus 0.15 +/- 0.09 mm(3), P = 0.001), but not incidence (71% versus 100%, P = ns), compared with control. As vandetanib has other activities besides VEGFR-2 tyrosine kinase inhibition, we gave t...Continue Reading
References
May 4, 1989·Nature·J FolkmanD Hanahan
Sep 1, 1996·Cancer·L TongC A Amos
Oct 14, 1998·Cancer Metastasis Reviews·L WitteP Böhlen
Nov 24, 1999·Molecular Carcinogenesis·C JiangJ Lu
Mar 20, 2003·Journal of the National Cancer Institute·Peter B BachColin B Begg
Mar 5, 2004·Cancer Research·Yian WangMing You
Aug 18, 2004·Cancer Research·Robert L KeithMark W Geraci
Dec 23, 2004·JAMA : the Journal of the American Medical Association·Steinn JonssonKari Stefansson
Feb 16, 2005·Annals of Internal Medicine·Nicholas R AnthonisenUNKNOWN Lung Health Study Research Group
Mar 22, 2005·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Daniel T MerrickWilbur A Franklin
Nov 30, 2005·The American Journal of Pathology·Robert S StearmanMark W Geraci
Dec 17, 2005·Cancer Research·Nobukazu FujimotoJonathan M Kurie
Dec 26, 2006·Molecular Cancer Research : MCR·Ying YanMing You
Feb 17, 2007·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·Douglas M NoonanAdriana Albini
Mar 30, 2007·Cancer Chemotherapy and Pharmacology·Daniel L GustafsonDavid Raben
Jul 27, 2007·Proceedings of the National Academy of Sciences of the United States of America·Amir AbdollahiPeter E Huber
Oct 9, 2007·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Tariq A Bhat, Rana P Singh
Jan 18, 2008·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Tim ByersTimothy C Kennedy
Mar 19, 2008·Molecular Cancer Therapeutics·Denis AlferezRobert A Goodlad
Jun 20, 2008·Cancer Science·Kadoaki OhashiKatsuyuki Kiura
Jan 14, 2009·Cancer Prevention Research·Ximing TangIgnacio I Wistuba
Jan 14, 2009·Cancer Prevention Research·Raphael NemenoffRobert L Keith
Jan 21, 2009·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Daizo KishinoMitsune Tanimoto
Feb 3, 2009·Critical Reviews in Oncology/hematology·Zaher K OtrockAli I Shamseddine
May 29, 2009·CA: a Cancer Journal for Clinicians·Ahmedin JemalMichael J Thun
Jul 9, 2009·Cancer Prevention Research·Yian WangMing You
Aug 20, 2009·Cancer Research·Kadoaki OhashiKatsuyuki Kiura
Citations
Apr 2, 2013·Archives of Pharmacal Research·So-Hee ChunChaekyun Kim
Feb 7, 2014·EMBO Molecular Medicine·Marta LarrayozJackeline Agorreta
Dec 20, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ji-young KimYoungro Byun
Jun 12, 2016·Pharmacology & Therapeutics·Beverly L FalconBronislaw Pytowski
May 22, 2013·Nature Reviews. Clinical Oncology·Robert L Keith, York E Miller
Jun 16, 2012·Cancer Prevention Research·Vijaya KaroorYork E Miller
Nov 7, 2015·Cancer Prevention Research·Daniel T MerrickWilbur A Franklin
Jul 13, 2018·Cancer Research·Daniel T MerrickRaphael A Nemenoff