Date of Award

2015

Degree Name

Biomedical Sciences

College

Joan C. Edwards School of Medicine

Type of Degree

Ph.D.

Document Type

Dissertation

First Advisor

Pier Paolo Claudio

Second Advisor

Jagan Valluri

Third Advisor

W. Elaine Hardman

Fourth Advisor

Richard Niles

Fifth Advisor

Beverly Delidow

Abstract

There is a growing need (in the medical field) to design personalized therapy for cancer patients. Decades of cancer research have found no silver bullet that can cure all or even most patients. This study evaluated four patients affected by central nervous system (CNS) tumors (Ependymoma and Glioblastoma), and found that tumors with the same histology had unique responses to treatment. Each sample presented different levels of heterogeneity in expressed biomarkers and responded to drugs at varying levels.

Oncologists conventionally treat cancer patients with drugs tested in large clinical trials. However, often patients do not experience positive outcomes following treatments with standardof- care first line drugs and oncologists need to treat them with a different second-line anticancer therapy that is chosen empirically. This study was designed to find a way to better predict patient’s response to chemotherapeutic drugs. The focus of this study was on Central Nervous System (CNS) tumors because of their limited response to anticancer drugs and their low survival rate. The uniqueness of this study revealed that each patient’s tumor had different drug sensitivities and that screening for multiple drugs may increase the chance of finding a drug from which the patient would have the most benefit.

More importantly this study evaluated the Cancer Stem-Like Cell (CSLC) population sensitivity to these drugs. This subpopulation is responsible for initiation and maintenance of the tumor and is known to be resistant to chemotherapy drugs. Dr. Claudio’s laboratory developed a test capable of determining the cytotoxic drug to which cancer cells and CSLCs of an individual tumor are most responsive. In the future this procedure may focus the treatment of CNS patients to drugs effective against their particular tumor allowing them to have better outcomes with fewer detrimental side effects.

Subject(s)

Cancer - Treatment - Research.

Stem cells - Research.

Central nervous system - Cancer.

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