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Published online: 18 August 2013
© The Author(s) 2013. This article is published with open access at Springerlink.com
Abstract Survivin is a well-established target in experimental cancer therapy. The molecule is over-expressed in most human tumors, but hardly detectable in normal tissues. Multiple functions in different subcellular compartments have been assigned. It participates in the control of cell division, apoptosis, the cellular stress response, and also in the regulation of cell migration and metastasis. Survivin expression has been recognized as a biomarker: high expression indicates an unfavorable prognosis and resistance to chemotherapeutic agents and radiation treatment. Survivin is an unconventional drug target and several indirect approaches have been exploited to affect its function and the phenotype of survivin-expressing cells. Interference with the expression of the survivin gene, the utilization of its messenger RNA, the intracellular localization, the interaction with binding partners, the stability of the survivin protein, and the induction of survivin-specific immune responses have been taken into consideration. A direct strategy to inhibit survivin has been based on the identification of a specifically interacting peptide. This peptide can recognize survivin intracellularly and cause the degradation of the ligand-survivin complex. Technology is being developed that might allow the derivation of small molecular-weight, drug-like compounds that are functionally equivalent to the peptide ligand.
1 Introduction
1.1 Progress in Tumor Therapy and Properties of Desirable Drug Targets
Progress in prevention and therapy has led to remarkable decreases in mortality and death rates due to cancer. Between 1990 and 2008, the death rates declined by 15.1 % in women and 22.9 % in men [1, 2]. Preventive measures, extensive screening programs for breast and colon cancer, and the development of new and effective drugs contributed to these reductions. Studies of the genetic basis of cancer, insights into the regulation of signaling pathways and their biochemical components, understanding the communication between cancer cells and normal cells, and the elucidation of the mechanisms of metastasis are areas in which basic research has made remarkable progress. This knowledge led to the identification and exploitation of new and promising drug targets. Molecularly targeted therapies, aimed at individual signaling components activated in cancer cells, have improved the success of treatment [3, 4].
Following the pioneering example set by the inhibition of the...