All ETDs from UAB

Advisory Committee Chair

Charles N Landen

Advisory Committee Members

Robin G Lorenz

Ronald D Alvarez

Mary-Ann Bjornsti

Michael Conner

G Yancey Gillespie

Document Type

Dissertation

Date of Award

2014

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Ovarian cancer while the second most common gynecologic malignancy is the most commons cause of death due to a gynecologic malignancy and the fifth most common cause of death to cancer in women. In 2014, there will be an expected 21,980 cases and 14,270 deaths. Unfortunately, the five-year survival for ovarian cancer is only 40% and this has barely increased over the past 30 years. New approaches need to be developed in order to study ovarian cancer and identify methods of overcoming chemotherapy resistance. This dissertation presents the work conducted in the development of a patient-derived xenograft model of ovarian cancer to characterize the chemotherapy resistant population and identify novel methods of targeting ovarian cancer. The ovarian cancer patient-derived xenograft model recapitulates the heterogeneity of the patients' tumor and has demonstrated clinical relevance in response to primary therapy. Using RNA-seq, it was identified that ribosomal synthesis was up-regulated and targeting RNA Polymerase I is a potential method of overcoming chemotherapy resistance. Using a patient-derived xenograft model provides a novel platform for understanding chemotherapy resistance and recurrence in ovarian cancer.

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