SPARC: A Potential Prognostic and Therapeutic Target in Pancreatic Cancer

被引:93
作者
Vaz, Juan [1 ]
Ansari, Daniel [1 ]
Sasor, Agata [2 ]
Andersson, Roland [1 ]
机构
[1] Lund Univ, Skane Univ Hosp, Clin Sci Lund, Dept Surg, SE-22185 Lund, Sweden
[2] Lund Univ, Skane Univ Hosp, Clin Sci Lund, Dept Pathol, SE-22185 Lund, Sweden
关键词
albumin-bound paclitaxel; pancreatic cancer; pathophysiological mechanisms; SPARC; stromal depletion; ALBUMIN-BOUND PACLITAXEL; PAPILLARY MUCINOUS NEOPLASMS; NAB-PACLITAXEL; EXTRACELLULAR-MATRIX; SECRETED PROTEIN; ABERRANT METHYLATION; DNA METHYLATION; POOR-PROGNOSIS; MESSENGER-RNA; CLINICAL-SIGNIFICANCE;
D O I
10.1097/MPA.0000000000000409
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Pancreatic cancer is a complex and heterogeneous disease that often lacks disease-specific symptoms in early stages. The malignancy is currently the fourth leading cause of cancer-related death in Western countries. In advanced stages, the overall 5-year survival is less than 1% to 2%. Most available treatments lack convincing cost-efficiency determinations and are generally not associated with relevant success rates. Targeting stromal components and stromal depletion is currently becoming an area of extensive research in pancreatic cancer. In this context, a glycoprotein, SPARC (secreted protein acidic and rich in cysteine) appears to play a central role. Still, the role of SPARC in carcinogenesis is controversial because conflicting results have been reported, and the pathways involved in SPARC signaling are not well established. Nonetheless, SPARC is highly expressed in the tumor stroma, principally in peritumoral fibroblasts, and the overexpression of SPARC in this compartment is associated with poorer prognosis. Interestingly, it has been suggested that SPARC present in the tumor stroma could sequester albumin-bound paclitaxel, enhancing the delivery of paclitaxel into the tumor microenvironment. In the present review, we summarize the known associations between SPARC and pancreatic cancer. Moreover, present and future therapies comprising SPARC-targeting are discussed.
引用
收藏
页码:1024 / 1035
页数:12
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