Emerging strategies for delivering antiangiogenic therapies to primary and metastatic brain tumors

Five-year survival rates have not increased appreciably for patients with primary and metastatic brain tumors. Nearly 17,000 patients die from primary brain tumors, whereas approximately 200,000 cases are diagnosed with brain metastasis every year in the US alone. At the same time, with improved control of systemic disease, the incidence of brain metastasis is increasing. Thus, novel approaches for improving the treatment outcome for these uniformly fatal diseases are needed urgently. In the review, we summarize the challenges in the treatment of these diseases using antiangiogenic therapies alone or in combination with radio-, chemo- and immuno-therapies. We also discuss the emerging strategies to improve the treatment outcome using both pharmacological approaches to normalize the tumor microenvironment and physical approaches (e.g., focused ultrasound) to modulate the blood-tumor-barrier, along with limitations of each approach. Finally, we offer some new avenues of future research.