Identification of Therapeutic Targets and Molecular Markers for Glioblastoma Stem Cells.

摘要

Glioblastoma Multiforme (GBM) is the most common type of malignant brain cancer with a median survival of only 14 months post diagnosis. The current standard of care for all the patients is maximal surgical resection followed by radiation and chemotherapy with temozolomide, a DNA alkylating agent. This treatment reduces the tumor bulk, but is not curative as recurrence is very common. The GBM tumor cell population is heterogeneous and a small percentage of the tumor cell population, known as GBM stem cells (GBM-SCs), has the capacity to initiate and sustain tumor growth as well as the ability to survive in hypoxic tumor niches. Hypoxia drives clonogenicity of GBM-SCs and increases their ability to resist chemo and radiotherapy. GBM-SCs can be isolated using cell surface markers such as CD133. However, these markers are not ideal, as they do not detect all the cancer stem cell populations and their expression can change in response to the external microenvironment, which may lead to confounding results.;Due to the high mortality associated with these tumors, there is an urgent need for the development of new therapeutics against GBM and especially ones that specifically target the GBM-SC population. Further, the lack of good GBM stem cell markers is a hindrance to our ability to identify and study these cells. In this thesis, I have identified novel therapeutic targets for GBM-SCs and have characterized novel molecular markers for GBM-SCs. (Abstract shortened by ProQuest.).