title: Targeting survivin in cancer: novel drug development approaches.
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.
authors: Georg Speyer Haus, Institute for Biomedical Research, Paul Ehrlich Str. 42, 60322, Frankfurt am Main, Germany, groner@em.uni-frankfurt.de.
authors: Bernd
authors: B
authors: Groner
authors: Astrid
authors: A
authors: Weiss
mesh_terms: D015195:Drug Design; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D008024:Ligands; D058990:Molecular Targeted Therapy; D008970:Molecular Weight; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008024:Ligands; D010455:Peptides; D054852:Small Molecule Libraries; D000077022:Survivin
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