Inhibitor of apoptosis proteins: new therapeutic targets in hematological cancer?

Apoptosis is an essential process for the selection and survival of lymphocytes. Resistance to apoptosis can promote malignant transformation of hematopoietic cells. Proteins that regulate apoptosis may therefore be critically involved in the development of hematological cancer. A delicate balance between pro- and antiapoptotic mechanisms determines whether a cell death signal can activate the execution of the apoptotic cell death program. The family of inhibitor of apoptosis (IAP) proteins is a recently identified, novel category of apoptosis-regulatory proteins. IAPs can inhibit the activation of caspases that are the executioners of apoptosis, activated by both the extrinsic and intrinsic pathway. IAPs may thereby set the threshold for apoptosis-activation and play a key role in the regulation of apoptotic cell death. IAPs themselves are also subject to strict regulation through feedback mechanisms. This paper focuses on the role of IAP family proteins in the regulation of apoptosis and discusses implications for their involvement in cancer and possible use for cancer therapy, especially in leukemias and lymphomas.