ABSTRACT
Tumor vasculature plays an important role in facilitating the continuous growth and survival of solid tumors. For tumors to fulfill their metabolic demands of nutrients and oxygen, new blood vessels are formed from the pre-existing ones. These newly formed vessels are highly disorganized and morphologically abnormal. Studies suggest that aberrant tumor blood vessels are more susceptible to radiation. Typically, radiation therapy with radiation dose higher than 10 Gy, also known as stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT), can cause direct tumor cell death as a result of DNA damage. Secondary or indirect cell death occurs due to the massive deterioration of tumor vasculature regulated by the acid sphingomyelinase/ceramide pathway following a high dose of radiation. Tumor cell death induced by high-dose radiation further stimulates the immune response by releasing tumor-specific antigens. Studies have indicated that modulating tumor vasculature by combining targeted therapies can potentiate the effect of radiation. In this chapter, we will discuss the cellular targets, biological effects, and the underlying possible mechanisms of high-dose radiotherapy drawn mostly from in vitro and in vivo studies. A brief overview of recent advancement in combining radiation with vascular targeted therapies will also be discussed.
