Identification of the Hedgehog pathway as a novel therapeutic target in malignant gliomas

Abstract

Gliomas are the predominant type of primary central nervous system tumors. They are highly invasive and notoriously refractory to current therapies. Patients diagnosed with a malignant glioma face a dismal prognosis that has remained relatively unchanged in the last three decades. A promising novel approach to glioma therapy is based upon modulating molecular mechanisms that regulate cell types critical for tumor growth. Recent identification of cancer stem cells that initiate and maintain tumor growth in gliomas has prompted investigation into the molecular signaling pathways that regulate this unique cell type. The Hedgehog (Hh) signaling pathway regulates stem cells and is activated in several cancer types. Prompted by the role of Hh signaling in regulating neural stem cell self-renewal, I investigated the potential role of the pathway in glioma growth. To address this question, I evaluated the status of Hh signaling in primary gliomas. Furthermore, I tested our hypothesis that Hh signaling regulates glioma growth in a relevant preclinical model.