Gefitinib accumulation in glioblastoma tissue

Cancer Biol Ther. 2006 May;5(5):483-4. doi: 10.4161/cbt.5.5.2653. Epub 2006 May 5.


Therapeutic agents for brain tumors confront multiple physical and metabolic hurdles. These include the blood brain barrier (BBB), vascular and interstitial barriers, clearing by MDR1 and other ABC transporter proteins, and drug catabolism. Here, we report an accumulation of gefitinib in glioblastoma (GBM) tissue to over a dozen times plasma levels, and propose that some mechanisms converge to achieve such accumulation: (1) small molecular size of gefitinib facilitates access by diffusion; (2) its high water solubility enables thermodynamic retention inside malignant cells; and (3) low CYP3A4 activity in GBM tissue, the main enzyme for gefitinib catabolism, prevents metabolic elimination. Our data confirm the capacity of gefitinib to accumulate in solid human tumors in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism
  • ErbB Receptors / antagonists & inhibitors
  • Gefitinib
  • Glioblastoma / drug therapy
  • Glioblastoma / metabolism*
  • Humans
  • Mass Spectrometry
  • Quinazolines / metabolism*
  • Quinazolines / therapeutic use


  • Antineoplastic Agents
  • Quinazolines
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • ErbB Receptors
  • Gefitinib