Cancers of the brain are intrinsically more complicated to treat than systemic
malignancies due to the unique anatomical features of the brain. The blood-brain barrier prevents chemotherapeutic agents from reaching
brain neoplasms, and angiogenesis occurs as the metabolic needs of the tumour increase, thus further complicating treatment. The newly formed blood vessels form the blood-tumour barrier and are distinct from the blood-brain barrier in that they are more permeable. Being more permeable, these abnormal blood vessels lead to the formation of peri-tumoural
edema, which is the cause of much morbidity and mortality associated with
central nervous system neoplasms. While the cause of the increased permeability is unclear,
kinins have been implicated in regulating the permeability of normal vasculature.
Kinins are also known to exert many inflammatory actions affecting both normal and angiogenic blood vessels, as well as tumour cells. The vasodilatory and vascular permeabilizing effects of
kinins, and particularly
bradykinin and
substance P, have been investigated with regard to delivery of chemotherapeutic agents to neoplastic brain tissue through both vascular barriers. In contrast,
kinin receptor antagonists have been found to exert effects on tumour cells that result in decreased angiogenesis, tumour cell motility and growth. Thus, many recent patents describe
kinin activity on brain vasculature, which may play an integral role in the development of treatments for
malignancies in the central nervous system through amelioration of angiogenesis. In conjunction, patents that discuss the ability of
kinins to decrease tumour cell migration and proliferation demonstrate that
kinins may offer novel approaches to brain tumour
therapy in the future.