Document Type

Thesis

Publication Date

6-3-2019

Disciplines

Medical Molecular Biology | Medical Pharmacology | Pharmaceutics and Drug Design

Advisor

Katherine Leehy, Biology

Abstract

Ovarian cancer is the deadliest gynecologic malignancy in the United States. While these tumors may have a promising initial response to platinum-based chemotherapies, the patient’s prognosis is commonly hindered by the development of platinum resistant cancer. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been implicated as a potential treatment for many cancers based on its tumor selective nature. Combination therapies with TRAIL and platinum drugs have been shown to increase apoptosis and have been used in a variety of clinical trials, which have thus far failed to pass phase II.1 Researchers have not yet elucidated the complex mechanism(s) of TRAIL sensitivity. The objective of the following experiments was to investigate TRAIL sensitivity in paired isogenic platinum resistant and sensitive ovarian cancer cell lines. TRAIL induced cell death quantification, death receptor quantification, and protein analysis was carried out. While all platinum resistant cell lines (A2780 CP200, IGROV1 CP, PEO4, and ABTR2) were sensitive to TRAIL, their isogenic platinum sensitive counterparts (A2780, IGROV1, and PEO1) are much less sensitive. In an effort to elucidate the mechanism of sensitivity in the platinum-resistant lines, known mediators of the TRAIL induced killing pathway were quantified. TRAIL treatment should be considered for ovarian cancer patients who have experienced relapse after platinum-based chemotherapy.

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