Biomedical Sciences ETDs

Publication Date

12-1-2015

Abstract

Breast cancer is the second leading cause of cancer related deaths in women. Advanced breast cancer can metastasize to the lungs, liver, bones and brain becoming fatal conditions for many patients. There is a dire need for metastasis preventing medications, however the process required for a medication to become FDA approved for clinical use is long and arduous. Studies have found promising benefits for breast cancer patients given ToradolTM, or racemic ketorolac, as an NSAID during resection surgery. However, long-term use of racemic ketorolac is not recommended. Currently FDA-approved for use in the racemic form, ketorolac has the potential to become a valuable off-label drug for cancer patients, and if given as a single enantiomer, may not cause toxic effects. Recent work on ovarian cancer cell lines has shown (R)-ketorolac to have an effect on invasion and migration abilities via interaction with small Rho-GTPases. We hypothesized that (R)-ketorolac would likewise have the ability to inhibit breast cancer invasion and migration by binding to Cdc42, Rac1 and RhoA. The activity of racemic ketorolac and its enantiomers, (S)-ketorolac and (R)-ketorolac was studied in both in vivo and in vitro settings. In breast cancer cell lines it was shown that ketorolac does not affect the viability of cells, but does inhibit colony formation and migration. In MMTV-PyMT mouse models, ketorolac treatment does not appear to have toxic effects on the organism, and may prevent early mammary gland tumor growth and, in older mice, metastasis. These studies suggest that the (R)- enantiomer of ketorolac may be useful in preventing tumor growth and metastasis without imparting significant toxicities.

Keywords

breast cancer, cancer, ketorolac, metastasis, NSAID

Sponsors

National Institutes of Health (NIH) 1R21CA170375-01S

Document Type

Thesis

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Masters

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Hathaway, Helen

Second Committee Member

Prossnitz, Eric

Third Committee Member

Wandinger-Ness, Angela

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