Survivin as a prognostic/predictive marker and molecular target in cancer therapy

Department of Radiotherapy and Oncology, University of Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Current Medicinal Chemistry (Impact Factor: 3.85). 06/2012; 19(22):3679-88. DOI: 10.2174/092986712801661040
Source: PubMed

ABSTRACT Evasion from apoptotic cell death is reported to be a pivotal mechanism by which tumor cells acquire resistance to therapeutic treatment. Targeting the apoptotic pathways may constitute a promising strategy to counteract therapy resistance and to re-sensitize cancer cells. Expression of survivin, the smallest and structurally unique member of the inhibitor of apoptosis protein (IAP) family, has been shown to be associated with poor clinical outcome, more aggressive clinicopathologic features and resistance to both, conventional chemo and radiation therapy. Moreover, survivin detection in cancer tissue, in circulating tumor cells and in patient's serum has prognostic and predictive relevance and may display a prerequisite for marker based molecular therapies. Indeed, due to its universal over expression in malignant tissue, and its prominent role at disparate networks of cellular division, intracellular signaling, apoptosis and adaption to unfavorable surroundings, survivin has been shown to be a suitable target for a targeted therapy. The applicability of survivindriven strategies in clinical practice is currently under investigation as the first survivin antagonists (small molecule inhibitors, antisense oligonucleotides and immunotherapy) successfully entered phase I/II trials. Taken together, these data provide a rationale for the implementation of both, survivin as a molecular diagnostic tool and survivin targeted therapies, within future clinical practice.

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    • "Recently, we also reported that cervical carcinoma cells can secrete Survivin, generating an encapsulated extracellular pool of Survivin which can be taken up by other cancer cells enhancing their anti-apoptotic, proliferative, and metastatic potential [11] [12]. Currently, three therapeutic strategies targeting survivin in cancer through immunotherapy, small molecule inhibitors, or antisense oligonucleotides are being evaluated or have completed Phase II clinical trials [13] "
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