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A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
09:04

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors

Published on: March 15, 2016

An overview of small-molecule inhibitors of VEGFR signaling

S Percy Ivy1, Jeannette Y Wick, Bennett M Kaufman

  • 1Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA. ivyp@ctep.nci.nih.gov

Nature Reviews. Clinical Oncology
|September 9, 2009
PubMed

Insights

Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors show broad use in treating various cancers. This review details 44 VEGFR inhibitors in development, their pharmacokinetics, clinical trial status, and adverse events.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors are widely used for metastatic renal-cell carcinoma, gastrointestinal stromal tumors, and hepatocellular carcinoma.
  • These inhibitors are under development for numerous other cancers, including colorectal, lung, pancreatic, thyroid, ovarian, breast cancers, and sarcomas.

Purpose of the Study:

  • To review the structure-activity relationships of 44 VEGFR inhibitors in development.
  • To provide an overview of their pharmacokinetic profiles and developmental stages.
  • To detail Phase III clinical trials for licensing and efficacy, including disease studied, trial design, endpoints, and patient accrual.

Main Methods:

  • Review of 44 VEGFR inhibitors in development.
  • Analysis of pharmacokinetic profiles and developmental stages.
  • Compilation of data from Phase III clinical trials, including combination therapies and adverse events in 3,060 patients from National Cancer Institute-sponsored trials.

Main Results:

  • Detailed structure-activity relationships and pharmacokinetic profiles of 44 VEGFR inhibitors are outlined.
  • Phase III trial designs, endpoints, and accrual data are presented for specific indications.
  • On-target and off-target adverse events were analyzed for a subset of agents, with on-target effects mechanistically linked to VEGFR inhibition.

Conclusions:

  • Small-molecule VEGFR inhibitors are active across a range of malignancies.
  • These agents represent a unique therapeutic niche in cancer treatment.
  • On-target adverse events are predictable based on VEGFR inhibition mechanisms.

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