Target inhibition in antiangiogenic therapy a wide spectrum of selectivity and specificity

Ronan J. Kelly, Colleen Darnell, Olivier Rixe

Research output: Contribution to journalReview articlepeer-review

Abstract

Recent studies have revealed a previously unsuspected degree of vascular specialization within the host tissue and a tumor's microenvironment. The "vascular zip code" has been used to describe the unique expression of cell-surface molecules found in each vascular bed. Characterization of tumor blood vessels includes selective overexpression of a heterogenous group of proteins such as proteases, integrins, growth factor receptors, and proteoglycans. The process of angiogenesis consists of a "true cytokine storm," requiring many molecular events and biological steps. Antiangiogenic drugs may target a single critical kinase pathway or may interact with several nonspecific molecular targets via a process termed extended spectrum kinase inhibition. The latter strategy may lead to an absence of selectivity and specificity and may result in enhanced toxicities. In this review, we discuss recent developments in the pathogenesis of commonly observed adverse events and summarize new strategies that may ultimately improve efficacy and limit toxicity.

Original languageEnglish (US)
Pages (from-to)635-642
Number of pages8
JournalCancer Journal
Volume16
Issue number6
DOIs
StatePublished - Nov 1 2010

Keywords

  • Vascular endothelial growth factor
  • on/off target
  • selective
  • specific

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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