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Drug Resistance in Breast Cancer: Characterization of Rationally Designed Paclitaxel Analogs in Model Systems

  • Author / Creator
    St.George, Marc C
  • Breast cancer is a leading cause of cancer related deaths among
    women in the developed world. Treatment options for breast cancer
    include taxanes, which mediate cytotoxic effects by inducing microtubule
    polymerization which impedes cell division. Taxane resistant breast cancer
    is a mounting clinical problem, and can in part be explained by differential
    expression of -III tubulin and/or multidrug efflux pumps. I hypothesized
    that drugs traverse to the taxane active site through interactions at 275
    and 278 residues (intermediate binding sites) within microtubule nanopores.
    I developed paclitaxel resistant SKBR-3 cell sub-lines, used
    synthesized paclitaxel analogs designed to interact with the suggested
    residues and attempted to dissect the progression of resistance by
    monitoring global microRNA profiles. Data did not favour interpretations on
    the hypothesized interactions with amino acid residues; evidence
    suggested that expression of -III tubulin alone does not explain drug
    resistance and a combination of mechanisms likely mediates resistance.

  • Subjects / Keywords
  • Graduation date
    Fall 2013
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R33N20P02
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.