Degree Name

BS

Department

Physiology and Developmental Biology

College

Life Sciences

Defense Date

2018-11-29

Publication Date

2018-12-03

First Faculty Advisor

Marc Hansen

First Faculty Reader

Stephen Piccolo

Honors Coordinator

Roy Silcox

Keywords

ovarian cancer, drug resistance, microtubule targeting agent, tubulin, inhibitor, destabilizing agent

Abstract

Drug resistance remains problematic for chemotherapy treatments. As primary treatment strategies tend to lose potency against cancer, there is a need for treatment options that overcome drug resistance mechanisms. FROST450, a novel microtubule destabilizing agent, has proven anticancer effects that overcome taxane and multidrug resistance. However, to better understand the clinical potential of FROST450, in this study we examine the mechanisms and implications of acquired FROST450 resistance in an A2780 ovarian cancer cell line. Results indicate FROST450 resistance is associated with increased mitochondrial respiration and with changes in gene sequence or expression level of proteins associated with microtubules, and that these mechanisms do not confer cross-resistance to other common microtubule targeting agents. In addition, our findings suggest a differentiation between short- and long-term drug resistance mechanisms. Resultantly, FROST450 has the potential to be an important treatment option for cancer patients.

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