• DocumentCode
    1496166
  • Title

    Multiobjective Optimization Based-Approach for Discovering Novel Cancer Therapies

  • Author

    Mahoney, A.W. ; Podgorski, G.J. ; Flann, N.S.

  • Author_Institution
    Comput. Sci. Dept., Utah State Univ., Logan, UT, USA
  • Volume
    9
  • Issue
    1
  • fYear
    2012
  • Firstpage
    169
  • Lastpage
    184
  • Abstract
    Solid tumors must recruit new blood vessels for growth and maintenance. Discovering drugs that block tumor-induced development of new blood vessels (angiogenesis) is an important approach in cancer treatment. The complexity of angiogenesis presents both challenges and opportunities for cancer therapies. Intuitive approaches, such as blocking VegF activity, have yielded important therapies. But there maybe opportunities to alter nonintuitive targets either alone or in combination. This paper describes the development of a high-fidelity simulation of angiogenesis and uses this as the basis for a parallel search-based approach for the discovery of novel potential cancer treatments that inhibit blood vessel growth. Discovering new therapies is viewed as a multiobjective combinatorial optimization over two competing objectives: minimizing the estimated cost of practically developing the intervention while minimizing the simulated oxygen provided to the tumor by angiogenesis. Results show the effectiveness of the search process by finding interventions that are currently in use, and more interestingly, discovering potential new approaches that are nonintuitive yet effective.
  • Keywords
    biological techniques; blood vessels; cancer; cellular biophysics; drug delivery systems; optimisation; tumours; angiogenesis; blocking VegF activity; blood vessel growth; cancer therapy; cancer treatment; drugs; high-fidelity simulation; multiobjective optimization based-approach; parallel search-based approach; solid tumors; tumor-induced development; Biology computing; Blood vessels; Cancer; Computational modeling; Drugs; High performance computing; Medical treatment; Neoplasms; Pipelines; Recruitment; CPM; Cancer therapy; GGH; Glazier-Graner-Hogeweg model; VegF.; angiogenesis; cellular Potts model; computational discovery; multiobjective optimization; parallel search; Algorithms; Angiogenesis Inhibitors; Biomedical Research; Computational Biology; Computer Simulation; Drug Discovery; Humans; Models, Biological; Monte Carlo Method; Neoplasms; Neovascularization, Pathologic; Vascular Endothelial Growth Factor A;
  • fLanguage
    English
  • Journal_Title
    Computational Biology and Bioinformatics, IEEE/ACM Transactions on
  • Publisher
    ieee
  • ISSN
    1545-5963
  • Type

    jour

  • DOI
    10.1109/TCBB.2010.39
  • Filename
    5467037