- 381 views
- 308 downloads
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
-
- 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.