A perspective on vascular disrupting agents that interact with tubulin

Preclinical tumor imaging and biological assessment

Ralph P. Mason, Dawen Zhao, Li Liu, Mary Lynn Trawick, Kevin G. Pinney

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

The tumor microenvironment provides a rich source of potential targets for selective therapeutic intervention with properly designed anticancer agents. Significant physiological differences exist between the microvessels that nourish tumors and those that supply healthy tissue. Selective drug-mediated damage of these tortuous and chaotic microvessels starves a tumor of necessary nutrients and oxygen and eventually leads to massive tumor necrosis. Vascular targeting strategies in oncology are divided into two separate groups: angiogenesis inhibiting agents (AIAs) and vascular disrupting agents (VDAs). The mechanisms of action between these two classes of compounds are profoundly distinct. The AIAs inhibit the actual formation of new vessels, while the VDAs damage and/or destroy existing tumor vasculature. One subset of small-molecule VDAs functions by inhibiting the assembly of tubulin into microtubules, thus causing morphology changes to the endothelial cells lining the tumor vasculature, triggered by a cascade of cell signaling events. Ultimately this results in catastrophic damage to the vessels feeding the tumor. The rapid emergence and subsequent development of the VDA field over the past decade has led to the establishment of a synergistic combination of preclinical state-of-the-art tumor imaging and biological evaluation strategies that are often indicative of future clinical efficacy for a given VDA. This review focuses on an integration of the appropriate biochemical and biological tools necessary to assess (preclinically) new small-molecule, tubulin active VDAs for their potential to be clinically effective anticancer agents.

Original languageEnglish (US)
Pages (from-to)375-387
Number of pages13
JournalIntegrative Biology
Volume3
Issue number4
DOIs
StatePublished - Apr 2011

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Tubulin
Blood Vessels
Tumors
Imaging techniques
Neoplasms
Microvessels
Antineoplastic Agents
Cell signaling
Tumor Microenvironment
Molecules
Oncology
Endothelial cells
Microtubules
Set theory
Linings
Nutrients
Necrosis
Endothelial Cells
Oxygen
Food

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Cite this

A perspective on vascular disrupting agents that interact with tubulin : Preclinical tumor imaging and biological assessment. / Mason, Ralph P.; Zhao, Dawen; Liu, Li; Trawick, Mary Lynn; Pinney, Kevin G.

In: Integrative Biology, Vol. 3, No. 4, 04.2011, p. 375-387.

Research output: Contribution to journalArticle

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