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- W2061515040 abstract "Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCSurvivin, a protein highly expressed in human cancers is involved in both control of cell cycle progression and inhibition of apoptosis. Transcription of the survivin gene locus (BIRC-5) yields at least 5 alternative splice variants that have been designed survivn-WT, survivin-ΔEx3, survivin-2β, surivivn-3β, and survivin 2α. It has been shown that the survivin splice variants have different expression levels and subcellular localization patterns that could be associated with unique functional properties. Whereas the effects of survivin on apoptosis and mitosis have been extensively studied and explored therapeutically, the role of specific survivin splice variants in ovarian cancer has not been investigated. Our compelling studies indicate that, compared with their taxane-sensitive counterparts, taxane-resistant ovarian cancer cells express higher survivin mRNA (particularly the WT, ΔEx3 and 2β isoforms) levels. Studies have shown that survivin-2β has proapoptotic properties: whereas, forced expression of survivin-2β sensitized cells to taxane-induced apoptosis, small-interference RNA (siRNA)-based silencing of survivin-2β protected cells from cells from apoptotic cell death. We have observed opposite results: siRNA-based silencing of survivin-2β induced cell growth arrest and apoptosis of taxane-resistant ovarian cancer cells. Furthermore, liposomes-encapsulated siRNA targeting survivin-2β inhibited tumor growth in orthotopic murine models of ovarian cancer. The anti-tumor effect was further increased by combination with docetaxel. Finally, we found a significant association of survivin-2β expression with progression free survival in the 117 epithelial ovarian cancers obtained at primary debulking therapy. Further studies are necessary to clarify the role of survivin-2β in ovarian cancer. The key finding from our study is that survive-2β is present in a substantial proportion of ovarian cancers, and is predictive of decreased progression-free survival (PFS) of ovarian cancer patients. These studies also show the feasibility of survivin-2β-targeting siRNA liposomal as a clinically applicable therapeutic modality for taxane-resistant ovarian cancer.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 677." @default.
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- W2061515040 date "2010-04-15" @default.
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- W2061515040 title "Abstract 677: Targeting the survivin splice variant 2β in taxane-resistant ovarian cancer" @default.
- W2061515040 doi "https://doi.org/10.1158/1538-7445.am10-677" @default.
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