Blocking survivin to kill cancer cells.

Abstract

It has long been appreciated that dysregulation of apoptosis, or programmed cell death, plays a critical role in the onset and progression of cancer (). For the complexity of cell death pathways, this may result from deregulated overexpression of apoptosis inhibitors or loss/underrepresentation of apoptosis inducers. The net effect for both conditions is an aberrantly extended cell viability, which facilitates the acquisition of transforming mutations and the insurgence of chemoresistance (). Because of the tremendous progress recently made in elucidating apoptotic mechanisms and their relevance to human diseases, concrete therapeutic efforts are now underway to manipulate cell death pathways and eliminate survival signals that may contribute to keeping cancer cells alive (). To make an ideal drug target, an apoptosis regulator should be preferentially expressed in tumor cells but not in normal tissues, and interference with its expression/function should be sufficient to facilitate cell death, either alone, or in combination with chemotherapeutic drugs or ultraviolet/γ-irradiation. Data recently appeared in the literature suggests that the human survivin gene may fulfill both of these prerequisites. Furthermore, initial evidence in vitro and in vivo has suggested that targeting survivin may provide a viable approach to kill cancer cells selectively.