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Primary brain tumors and angiogenesis (Master thesis)

Κωνσταντινίδου, Ναταλία/ Konstantinidou, Natalia

Primary brain tumors – benign or malignant – are highly vascularized tumors. Hypoxic conditions and other characteristics of tumor microenvironment result in the predominance of signaling pathways that promote angiogenesis, the formation of new blood vessels from pre-existing vessels, which provides tumors with oxygen and the necessary nutrients. This process results in the uncontrolled and disorganized formation of blood vessels, which are characterized by the disturbance of blood-brain barrier and the increase of vascular permeability. Undoubtedly, angiogenesis plays a pivotal role in brain tumor growth and progression and therefore, constitutes a therapeutic target in neuro-oncology, although, no actual clinical benefit has been demonstrated to patients’ overall survival. To date, antiangiogenic agents are used as an adjunctive therapy by enhacing the standard treatment through the induction of normalization of the newly-formed blood vessels. However, the generated depletion of blood vessels enhances hypoxia in tumor microenvironment and guides tumor cells to recruit alternative mechanisms of vascularization, apart from angiogenesis, thus leading to increased tumor invasiveness and progression of the disease. Moreover, antiangiogenic drugs are associated with a variety of vascular complications, including ischemic and hemorrhagic stroke. However, the interplay between primary brain tumors and stroke is versatile. The initial manifestation of a brain tumor may mimic stroke and rarely, be an actual established stroke. Furthermore, primary brain tumors may predispose to an ischemic or hemorrhagic stroke through a plethora of mechanisms, related to patient, tumor or more often to cancer therapy. Conversely, there are indications that a medical history of cerebral infarct might constitute a risk factor for developing brain tumor. However, this hypothesis remains to be confirmed by further experimental and clinical studies. Primary brain tumors and stroke share common pathophysiological pathways as a response to hypoxia – one of which is angiogenesis, which may be the link between these two clinical entities.