review of literature on clinical pancreatology - The Pancreapedia

xenograft model <strong>of</strong> pancreatic cancer. With respect to a test <strong>of</strong> therapeutic effect, it is clearfrom preclinical studies that hedgehog inhibitors should be examined in combination withgemcitabine, the current standard <strong>of</strong> care for treatment. It has been suggested that thosepatients with locally advanced pancreatic cancer are the most likely to benefit from atherapeutic approach that involves inhibition <strong>of</strong> the hedgehog pathway. This subgrouprepresents up to 30 percent <strong>of</strong> patients at the time <strong>of</strong> diagnosis, and these patient have atype <strong>of</strong> cancer that is characterized by stroma-rich hypovascular tumors that cannot beresected because <strong>of</strong> large-vessel involvement [379].HSP27A prior study suggested serum heat shock protein 27 (HSP27) as a potential marker forpancreatic carcinoma, but its accuracy in differentiating cancer from chronic pancreatitis wasnot evaluated. Pretreatment serums from 58 pancreatic carcinoma, 44 chronic pancreatitis,and 102 control subjects were collected. Serum HSP27 and carbohydrate antigen 19-9(CA19-9) levels were analyzed using an enzyme-linked immunosorbent assay andradioimmunoassay, respectively. Heat shock protein 27 levels were significantly higher incancer and pancreatitis compared with control, but no significant difference was notedbetween cancer and pancreatitis. By logistic regression, HSP27 was a significant predictor <strong>of</strong>differentiation between cancer and control but not between cancer and pancreatitis. At acut<strong>of</strong>f <strong>of</strong> 1650 ng/L, the sensitivity and specificity for differentiating cancer from healthycontrol were 62 percent and 95 percent, respectively. Receiver operating characteristicanalyses showed a significantly greater area under curve for CA19-9 compared with HSP27in differentiating between cancer and control. It was thus concluded that serum HSP27 isincreased in both chronic pancreatitis and pancreatic carcinoma but it should not berecommended as a diagnostic marker for pancreatic carcinoma [380].HuRGemcitabine has been the standard <strong>of</strong> care for pancreatic cancer for a decade but is onlyeffective in some patients. As a prodrug, gemcitabine is activated by different proteinkinases. The deoxycytidine kinase (dCK) is the first step <strong>of</strong> intracellular activation. TStudieson the Hu antigen R (HuR), a stress response protein, on dCK expression and the correlationbetween HuR expression levels and pancreatic cancer outcome demonstrates that dCKprotein concentration levels were regulated by HuR and that a high cytoplasmic HuR levelwas associated with a sevenfold decreased risk <strong>of</strong> mortality after resection <strong>of</strong> pancreaticadenocarcinoma and gemcitabine therapy [381].IGF-1 receptorThe insulin-like growth factor 1 receptor (IGF-1R) and its associated signalling system hasprovoked considerable interest over recent years as a novel therapeutic target in cancer.There are in vitro and in vivo data in the published <strong>literature</strong> <strong>of</strong> the following compoundstargeting IGF-1R components using specific examples: growth hormone releasing hormoneantagonists (e.g. JV-1-38), growth hormone receptor antagonists (e.g. pegvisomant), IGF-1Rantibodies (e.g. CP-751,871, AVE1642/EM164, IMC-A12, SCH-717454, BIIB022, AMG 479,MK-0646/h7C10), and IGF-1R tyrosine kinase inhibitors (e.g. BMS-536942, BMS-554417,NVP-AEW541, NVP-ADW742, AG1024, potent quinolinyl-derived imidazo (1,5-a)pyrazinePQIP, picropodophyllin PPP, Nordihydroguaiaretic acid Insm-18/NDGA). Pancreatic canceris among the tumors that have been tested for response [382].IntegrinesFactors mediating the invasion <strong>of</strong> pancreatic cancer cells through the extracellular matrix