Targeting survivin in cancer therapy: Pre-clinical studies

Survivin is a structurally unique member of the inhibitor of apoptosis protein family that in addition to acting as a suppressor of programmed cell death also plays a central role in cell division. Owing to its massive up-regulation in human tumors and its involvement in cancer progression and treatment resistance, survivin is currently undergoing extensive investigation as a promising target for new anticancer interventions. Several preclinical studies have demonstrated that down-regulation of survivin expression or function, accomplished by means of various strategies (including the use of antisense oligonucleotides, small interfering RNAs, ribozymes, dominant negative mutants and small molecule antagonists), reduced tumor growth potential, increased the apoptotic rate, and sensitized tumor cells to chemotherapeutic drugs and ionizing radiation in different human tumor preclinical models. Moreover, the first survivin inhibitors have already reached the clinic with some promise. However, due to its documented role in some normal tissues, the possibility that survivin disruption could affect normal cell function, mainly the hematopoietic and immune systems, cannot be excluded. In this context, a better understanding of the effects exerted by survivin on normal versus malignant cells will be important for the design of optimal strategies to selectively disrupt survivin in cancer.