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Title: ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinase activity in combination with radiotherapy

Abstract

Radiation enhances both epithelial growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) expression, which are a part of key pathways for tumor progression. Some tumors may not respond well to EGFR inhibitors alone or may develop resistance to EGFR inhibitors. Therefore, drug therapy targeted to VEGF receptors and EGFRs, when combined with radiotherapy (RT), may improve tumor control and provide wider applicability. This article focuses on ZD6474, an inhibitor of EGFR and VEGF receptor signaling in combination with RT. We discuss preclinical and clinical studies with RT and inhibitors of VEGF or EGFR signaling first. We then address issues associated with ZD6474 pharmacokinetic dosing, and scheduling when combined with RT. We also discuss ZD6474 in the context of anti-EGFR therapy resistance. Dual inhibition of EGFR and VEGF receptor signaling pathways shows promise in enhancing RT efficacy.

Authors:
 [1];  [2];  [3];  [4];  [5];  [6]
  1. Department of Radiation Oncology, University of Colorado Health Sciences Center, Aurora, CO (United States)
  2. Department of Pharmacology, University of Colorado Health Sciences Center, Aurora, CO (United States)
  3. Dipartimento di Oncologia, dei Trapianti e delle Nuove Technologie in Medicina, Universita di Pisa, Pisa (Italy)
  4. Department of Molecular and Clinical Endocrinology, Universita degli Studi di Napoli Federico II, Naples (Italy)
  5. AstraZeneca, Wilmington, DE (United States)
  6. Department of Radiation Oncology, University of Colorado Health Sciences Center, Aurora, CO (United States). E-mail: david.raben@uchsc.edu
Publication Date:
OSTI Identifier:
20788263
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 1; Other Information: DOI: 10.1016/j.ijrobp.2005.05.050; PII: S0360-3016(05)00962-4; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; DRUGS; GROWTH FACTORS; INHIBITION; NEOPLASMS; RADIOTHERAPY; RECEPTORS; TYROSINE

Citation Formats

Frederick, Barbara, Gustafson, Dan, Bianco, Cataldo, Ciardiello, Fortunato, Dimery, Isaiah, and Raben, David. ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinase activity in combination with radiotherapy. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.0.
Frederick, Barbara, Gustafson, Dan, Bianco, Cataldo, Ciardiello, Fortunato, Dimery, Isaiah, & Raben, David. ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinase activity in combination with radiotherapy. United States. doi:10.1016/J.IJROBP.2005.0.
Frederick, Barbara, Gustafson, Dan, Bianco, Cataldo, Ciardiello, Fortunato, Dimery, Isaiah, and Raben, David. Sun . "ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinase activity in combination with radiotherapy". United States. doi:10.1016/J.IJROBP.2005.0.
@article{osti_20788263,
title = {ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinase activity in combination with radiotherapy},
author = {Frederick, Barbara and Gustafson, Dan and Bianco, Cataldo and Ciardiello, Fortunato and Dimery, Isaiah and Raben, David},
abstractNote = {Radiation enhances both epithelial growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) expression, which are a part of key pathways for tumor progression. Some tumors may not respond well to EGFR inhibitors alone or may develop resistance to EGFR inhibitors. Therefore, drug therapy targeted to VEGF receptors and EGFRs, when combined with radiotherapy (RT), may improve tumor control and provide wider applicability. This article focuses on ZD6474, an inhibitor of EGFR and VEGF receptor signaling in combination with RT. We discuss preclinical and clinical studies with RT and inhibitors of VEGF or EGFR signaling first. We then address issues associated with ZD6474 pharmacokinetic dosing, and scheduling when combined with RT. We also discuss ZD6474 in the context of anti-EGFR therapy resistance. Dual inhibition of EGFR and VEGF receptor signaling pathways shows promise in enhancing RT efficacy.},
doi = {10.1016/J.IJROBP.2005.0},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 1,
volume = 64,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}