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Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
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Tumour vascular disrupting agents: combating treatment resistance

G M Tozer1, C Kanthou, G Lewis

  • 1University of Sheffield, Academic Unit of Surgical Oncology, K Floor, School of Medicine & Biomedical Sciences, Beech Hill Road, Sheffield S10 2RX, UK. g.tozer@sheffield.ac.uk

The British Journal of Radiology
|October 10, 2008
PubMed

Insights

Tubulin-binding agents, known as vascular disrupting agents (VDAs), show promise in cancer treatment by targeting tumor blood flow. Addressing treatment resistance through combination strategies is key to their effective use alongside conventional therapies.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Tubulin-binding microtubule-depolymerizing agents function as vascular disrupting agents (VDAs) in cancer therapy.
  • Several VDAs are undergoing clinical trials in combination with standard cancer treatments like chemotherapy and radiotherapy.

Purpose of the Study:

  • To provide an update on combretastatin-based VDAs.
  • To summarize their mechanisms of action.
  • To address treatment resistance issues, exemplified by disodium combretastatin A-4 3-O-phosphate (CA-4-P).

Main Methods:

  • Review of existing literature on tubulin-binding VDAs, focusing on combretastatins.
  • Analysis of mechanisms of action, including tumor blood flow shutdown.
  • Examination of treatment resistance factors, such as hypoxia and angiogenesis.

Main Results:

  • VDAs characteristically induce rapid shutdown of tumor blood flow with minimal impact on normal tissues.
  • Tumor rims exhibit relative resistance to VDA treatment.
  • Hypoxia and reoxygenation upregulate genes linked to angiogenesis and drug resistance.

Conclusions:

  • VDAs offer a novel approach to cancer treatment, complementing standard therapies.
  • Overcoming treatment resistance is crucial for maximizing VDA efficacy.
  • Combination strategies targeting hypoxia-induced resistance are a promising avenue.

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