In a crossover pharmacokinetic study to limit patient variability, nab-pacliataxel had higher peak plasma and unbound concentrations (88). Greater unbound fraction of paclitaxel has been hypothesized to lead to greater efficacy seen in many clinical trials. One possible mechanism of efficacy by the albumin-bound agent may be related to enhanced tumor uptake through interaction with the SPARC (secreted protein acid rich in cysteine) molecule. The SPARC gene, highly conserved among vertebrates, regulates the assembly, organization, and turnover of the extracellular matrix by binding and modulating the deposition of multiple structural Inhibitors,research,lifescience,medical components and

attenuating the activity of extracellular proteases. SPARC is expressed in cancer-associated stroma and in malignant cells

of some types, affecting tumor Lenalidomide FDA development, Inhibitors,research,lifescience,medical invasion, metastases, angiogenesis and inflammation. SPARC-induced changes in the tumor microenvironment can suppress or promote progression of different cancers depending on the tissue and cell type. SPARC expression is related to tumor aggressiveness though the exact mechanism is unclear. The molecule regulates the effects of bFGF and VEGF on MAPK signaling and increased expression of SPARC in pancreas Inhibitors,research,lifescience,medical tumors has been related to poorer survival (91),(92). Infante et al. characterized SPARC expression in peritumoral fibroblasts and pancreas cells from 299 patients Inhibitors,research,lifescience,medical with resectable pancreas cancer. Median survival was halved in patients’ tumors that expressed SPARC (15 months vs 30 months) and when cases were controlled for other prognostic factors (tumor size, positive lymph nodes, margin status, tumor grade, and age) the hazard ratio (HR) was significant (HR 1.89; 95% CI, 1.31 to 2.74). Therapies combining nab-paclitaxel with kinase assay gemcitabine are under investigation in pancreas cancer given Inhibitors,research,lifescience,medical the high expression of SPARC in pancreas cancer. Several studies are underway and preliminary result showed impressive responsive rate and encouraging survival outcome. In a phase I/II trial, 63 previously untreated metastatic

patients Dacomitinib were treated with nab-paclitaxel and gemcitabine and among the 49 evaluable patients, 1 achieved CR (2%), 12 PRs (24%) and 20 SD (41%) (clinical benefit rate 67%). The response rate and PFS correlated with SPARC expression by immunohistochemistry (89). A single institution retrospective review of this combination in neoadjuvant setting for borderline and unresectable patients confirmed the high response rate (69% PR and 23% SD). About 23% of patients in the study went on to surgical resection with curative intent (90). This regimen is being evaluated in a phase III randomized trial among patients with untreated metastatic pancreas cancer. Conclusion Despite advancement in anti-cancer therapeutics, treatment options remain limited and prognosis poor for patients with pancreas cancer.