Astrocytic tumors: role of antiapoptotic proteins

Apoptosis is a fundamental anti-neoplastic AQ1 mechanism to prevent tumorigenesis. Nearly all neoplastic changes during the development of a normal cell to a cancer cell, such as DNA-damage, oncogene activation or cell cycle deregulation, are potent inducers of the programmed cell death pathway. Therefore, overcoming the apoptotic failsafe is a key mechanism in the genesis and progression of tumors. In astrocytic brain tumors, the apoptotic failure has been documented and involves both the intrinsic or mitochondrial and extrinsic or receptor pathways of apoptosis. This breakdown may be caused by an imbalance of pro- and antiapoptotic members of the Bcl-2 protein family, inhibition of the activity of caspases by specific factors, changes in the p53 system. Detailed molecular knowledge of the anti-apoptotic mechanisms of astrocytic tumor cells is essential for the improvement of conventional chemotherapies and the development of new potent targeted therapies. In this chapter, authors describe the multiple antiapoptotic signals that have been demonstrated to be active in astrocytomas.