title: Stromal expression of SPARC in pancreatic adenocarcinoma.
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.
authors.affiliation: Department of Medical Oncology (INSERM U728-PRES Paris 7 Diderot), Beaujon University Hospital, Assistance Publique-Hôpitaux de Paris, 100 boulevard du Général Leclerc, 92110, Clichy-La-Garenne, France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Neuzillet
authors.forename: Annemilaï
authors.initials: A
authors.lastname: Tijeras-Raballand
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cros
authors.forename: Sandrine
authors.initials: S
authors.lastname: Faivre
authors.forename: Pascal
authors.initials: P
authors.lastname: Hammel
authors.forename: Eric
authors.initials: E
authors.lastname: Raymond
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D000418:Albumins / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D015676:Osteonectin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D000970:Antineoplastic Agents; D015676:Osteonectin; C577241:SPARC protein, human; D017239:Paclitaxel