Non-invasive evaluation of acute effects of tubulin binding agents: A review of imaging vascular disruption in tumors

Li Liu, Devin O’kelly, Regan Schuetze, Graham Carlson, Heling Zhou, Mary Lynn Trawick, Kevin G. Pinney, Ralph P. Mason

Research output: Contribution to journalReview articlepeer-review

Abstract

Tumor vasculature proliferates rapidly, generally lacks pericyte coverage, and is uniquely fragile making it an attractive therapeutic target. A subset of small-molecule tubulin binding agents cause disaggregation of the endothelial cytoskeleton leading to enhanced vascular permeability generating increased interstitial pressure. The resulting vascular collapse and ischemia cause downstream hypoxia, ultimately leading to cell death and necrosis. Thus, local damage generates massive amplification and tumor destruction. The tumor vasculature is readily accessed and potentially a common target irrespective of disease site in the body. Development of a therapeutic approach and particularly next generation agents benefits from effective non-invasive assays. Imaging technologies offer varying degrees of sophistication and ease of implementation. This review considers technological strengths and weaknesses with examples from our own laboratory. Methods reveal vascular extent and patency, as well as insights into tissue viability, proliferation and necrosis. Spatiotemporal resolution ranges from cellular microscopy to single slice tomography and full three-dimensional views of whole tumors and measurements can be sufficiently rapid to reveal acute changes or long-term outcomes. Since imaging is non-invasive, each tumor may serve as its own control making investigations particularly efficient and rigorous. The concept of tumor vascular disruption was proposed over 30 years ago and it remains an active area of research.

Original languageEnglish (US)
Article number2551
JournalMolecules
Volume26
Issue number9
DOIs
StatePublished - 2021

Keywords

  • Bioluminescence
  • Breast cancer
  • Combretastatins
  • Imaging
  • Inhibitors of tubulin polymerization
  • Kidney cancer
  • Lung cancer
  • Magnetic resonance imaging
  • Photoacoustics
  • Vascular disrupting agents

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Non-invasive evaluation of acute effects of tubulin binding agents: A review of imaging vascular disruption in tumors'. Together they form a unique fingerprint.

Cite this