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3 results

  • A review of vascular disrupting agents as a concomitant anti-tumour modality with radiation

  • William Tyler Tran, Ahmed El Kaffas, Azza Al-Mahrouki, Carol Gillies, Gregory Jan Czarnota
  • Journal:
    Journal of Radiotherapy in Practice / Volume 12 / Issue 3 / September 2013
    Published online by Cambridge University Press:
    02 May 2013, pp. 255-262
  • Background

    Tumour vasculature plays an important role in the development, maintenance and sustainability of a tumour. Endothelial cells which are recruited into the tumour stroma facilitate the formation of essential blood vessels that deliver nutrients and oxygen to tumour cells. A growing body of research is showing that there are synergistic anti-tumour effects when anti-vascular agents are combined with radiation. More recent reports have described favourable radiation response as a function of vascular targeting and blood vessel breakdown, primarily through interactions of radiation with vascular endothelial cells. Vascular disrupting agents are being utilised in several forms that include molecular targeting, biophysical assault and biological interference.

    Purpose

    In the present review, we examine current advances in anti-vascular agents to enhance tumour response when combined with radiation therapy.

    Methods

    A comprehensive literature search was conducted on the US National Library of Medicine, National Institutes of Health (PubMed) using the following search keywords: vascular disrupting agents, radiation sensitisation, anti-angiogenic therapy, anti-vascular therapy, radiation therapy.

    Conclusion

    Current research suggests the applicability of vascular disrupting agents as an effective radiation sensitisation agent. Pre-clinical and clinical trials have been well developed to form the theoretical framework to apply this powerful modality to the treatment of cancer.

  • A Computational Framework to Assess the Efficacy of CytotoxicMolecules and Vascular Disrupting Agents against Solid Tumours

  • M. Pons-Salort, B. van der Sanden, A. Juhem, A. Popov, A. Stéphanou
  • Journal:
    Mathematical Modelling of Natural Phenomena / Volume 7 / Issue 1 / 2012
    Published online by Cambridge University Press:
    25 January 2012, pp. 49-77
    Print publication:
    2012

  • A computational framework for testing the effects of cytotoxic molecules, specific to agiven phase of the cell cycle, and vascular disrupting agents (VDAs) is presented. Themodel is based on a cellular automaton to describe tumour cell states transitions fromproliferation to death. It is coupled with a model describing the tumour vasculature andits adaptation to the blood rheological constraints when alterations are induced by VDAstreatment. Several therapeutic protocols in two structurally different vascular networkswere tested by varying the duration of cytotoxic drug perfusion and the periodicity oftreatment cycles. The impact of VDAs were also tested both experimentally from intravitalmicroscopy through a dorsal skinfold chamber on a mouse and numerically. Simulationresults show that combining cytotoxic treatment with a post treatment of VDA through ajudicious timing could favour the rapid eradication of the tumour. The computationalframework thus gives some insights into the outcome of cytotoxic and VDAs treatments on aqualitative basis. Future validation from our experimental setup could open up newperspectives towards Computer-Assisted Therapeutic Strategies.

  • 10 - Antivascular therapy in gynaecological cancers

  • from SECTION 3 - IMAGING AND THERAPY: STATE OF THE ART
  • Edited by Sean Kehoe, Richard J. Edmondson, Martin Gore, Iain A. McNeish
  • Book:
    Gynaecological Cancers
    Published online:
    05 February 2014
    Print publication:
    01 June 2011, pp 121-138

  • Summary

    The great majority of women with advanced ovarian cancer will relapse and die from the disease. Angiogenesis is particularly relevant to ovarian cancer. Tumour vascular endothelial growth factor (VEGF) overexpression is associated with tumour angiogenesis, malignant progression and metastasis, ascites formation and early recurrence and death from the disease. Chemotherapy and vascular disrupting agents (VDAs) can cause mobilisation of bone marrow progenitor cells, including circulating endothelial progenitor cells (CEPs), which could theoretically increase angiogenesis. Two trials of combination therapy that included bevacizumab have suggested discrepancies between CA125 and RECIST response evaluation. VDAs selectively target pre-existing tumour vasculature, leading to rapid tumour cell ischaemia and death. The decrease in vascular tumour perfusion seen using dynamic contrast imaging suggests dynamic methods such as DCE-MRI, positron emission tomography-computed tomography (PET/CT) and MR spectroscopy in phase I and II trials may give an early indication of antivascular effect.