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Updated: Jul 10, 2026

A Novel High-resolution In vivo Imaging Technique to Study the Dynamic Response of Intracranial Structures to Tumor Growth and Therapeutics
12:09

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Published on: June 16, 2013

Improved tumor vascular function following high-dose epidermal growth factor receptor tyrosine kinase inhibitor

Mark M Moasser1, Lisa J Wilmes, Ching Hang Wong

  • 1Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA. mmoasser@medicine.ucsf.edu

Journal of Magnetic Resonance Imaging : JMRI
|October 31, 2007
PubMed
Abstract

Insights

Inhibitors targeting human epidermal growth factor receptor (HER) family tyrosine kinases can improve chemotherapy delivery. Gefitinib enhances paclitaxel efficacy by optimizing the tumor microenvironment and vascular function.

Area of Science:

  • Oncology
  • Cancer Biology
  • Pharmacology

Background:

  • Poor tumor vascular function impedes chemotherapy delivery and efficacy.
  • Human epidermal growth factor receptor (HER) family tyrosine kinases play a role in tumor vascular signaling.

Purpose of the Study:

  • To investigate if HER family inhibitors can enhance tumor vascular permeability and perfusion.
  • To determine if these inhibitors can optimize the efficacy of cytotoxic chemotherapeutics.

Main Methods:

  • BT474 human breast cancer xenografts were established in mice.
  • Dynamic contrast-enhanced MRI (DCE-MRI) assessed tumor vascular function.
  • Immunofluorescence microscopy evaluated tumor vascular architecture and perfusion following gefitinib treatment.

Main Results:

  • Gefitinib, a HER tyrosine kinase inhibitor (TKI), enhanced paclitaxel's antitumor activity in vivo, but not in cell culture.
  • A brief high dose of gefitinib decreased endothelial transfer constant (Kps) and increased tumor fractional plasma volume (fPV).
  • These vascular changes correlated with reduced tumor volume, decreased edema, and improved tumor vascular architecture and perfusion.

Conclusions:

  • HER family TKIs show potential for optimizing the tumor microenvironment.
  • This optimization may improve the delivery and efficacy of cytotoxic chemotherapeutics.

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