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Cancer and Metastasis Reviews

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01.12.2013 | NON-THEMATIC REVIEW

Stromal expression of SPARC in pancreatic adenocarcinoma

verfasst von: Cindy Neuzillet, Annemilaï Tijeras-Raballand, Jérôme Cros, Sandrine Faivre, Pascal Hammel, Eric Raymond

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 3-4/2013

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) stands as the poorest prognostic tumor of the digestive tract, with a 5-year survival rate of less than 5 %. Therapeutic options for unresectable PDAC are extremely limited and there is a pressing need for expanded therapeutic approaches to improve current options available with gemcitabine-based regimens. With PDAC displaying one of the most prominent desmoplastic stromal reactions of all carcinomas, recent research has focused on the microenvironment surrounding PDAC cells. Secreted protein acid and rich in cysteine (SPARC), which is overexpressed in PDAC, may display tumor suppressor functions in several cancers (e.g., in colorectal, ovarian, prostate cancers, and acute myelogenous leukemia) but also appears to be overexpressed in other tumor types (e.g., breast cancer, melanoma, and glioblastoma). The apparent contradictory functions of SPARC may yield inhibition of angiogenesis via inhibition of vascular endothelial growth factor, while promoting epithelial-to-mesenchymal transition and invasion through matrix metalloprotease expression. This feature is of particular interest in PDAC where SPARC overexpression in the stroma stands along with inhibition of angiogenesis and promotion of cancer cell invasion and metastasis. Several therapeutic strategies to deplete stromal tissue have been developed. In this review, we focused on key preclinical and clinical data describing the role of SPARC in PDAC biology, the properties, and mechanisms of delivery of drugs that interact with SPARC and discuss the proof-of-concept clinical trials using nab-paclitaxel.

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Titel: Stromal expression of SPARC in pancreatic adenocarcinoma
verfasst von: Cindy Neuzillet
Annemilaï Tijeras-Raballand
Jérôme Cros
Sandrine Faivre
Pascal Hammel
Eric Raymond
Publikationsdatum: 01.12.2013
Verlag: Springer US
Erschienen in: Cancer and Metastasis Reviews / Ausgabe 3-4/2013
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-013-9439-3

Springer Medizin

Stromal expression of SPARC in pancreatic adenocarcinoma

Abstract

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Abstract

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