Necroptosis: A novel therapeutic target for glioblastoma

Abstract

Glioblastoma or glioblastoma multiforme (GBM) is the most encountered and malignant form of brain tumors in clinical practice. In spite of optimal and early treatment, the life expectancy of patients with GBM remains poor. It is believed that dysfunction of apoptosis underlies GBM tumorigenesis, proliferation and resistance to chemotherapy and radiotherapy. Although GBM is defective in apoptotic process, pathologic and radiologic observations almost always reveal obvious necrosis foci within GBM. Necrosis seems to be related with GBM proliferation, angiogenesis and invasion. However, tumor cell necrosis induced by various therapies has a potential therapeutic value. Just recently, necrotic cell death is considered as a regulated and controlled process, like apoptosis, termed necroptosis or programmed necrosis. Induction of apoptosis has not made any significant achievements in the treatment of GBM mainly because the tumor cells are apoptosis-resistant. We may achieve a better result by modulating the necroptosis of GBM thus circumvent the apoptosis resistance. Albeit specific molecular pathways involved in GBM necroptosis is not clear and much more studies are needed to confirm the effects of therapy-induced necroptosis on GBM, it provides us with a new direction in the treatment of GBM.