re aberrantly expressed in many types of cancer including PD-1/PD-L1 inhibitor 2 manufacturer pancreatic cancer. Increased IGF-1R expression levels are associated with higher risk of developing various neoplasms. The IGF-1R signaling axis is highly activated during the early stages of lung carcinogenesis, where a role for IGF-1R signaling was demonstrated 
not only in primary tumor formation but also in progression to more aggressive lung adenocarcinoma. Jie Tang et al., 2013 reported high expression levels of IGF-1R in tumor tissue samples from 25 of 36 patients with epithelial ovarian cancer. They also reported consistently higher levels of IGF-1 in primary cancer cell cultures compared to normal ovarian tissue cell cultures . IGF-1R signaling activates intracellular signaling cascades that include phosphatidyl inositol 3-kinase, AKT, Rac and mitogen-activated protein kinase . These pathways regulate key genes involved in various cellular functions such as proliferation, survival, differentiation, transformation and apoptosis. Moreover, IGF-1R targets 70 1 Role of IGF-IR in Pancreatic Cancer to 100% of the core metabolic pathways that are often altered in PDAC pathogenesis. Targeting IGF-1R has already been shown to enhance the therapeutic effects of mTOR inhibitors in metastatic renal cell carcinoma,. Likewise, in human epithelial ovarian cancer, targeting IGF-1R by antisense nucleotide reduced proliferation by 70% and clonogenicity by 10 fold. In both in vitro and in vivo systems, an IGF-1R antagonist was shown to significantly down regulate X-linked inhibitor of apoptosis protein, which has been shown to be involved in cell survival and inhibition of cell death in colorectal cancer. Moreover, IGF-1R targeted therapies have already moved forward into phase I clinical trials for prostate, breast, colorectal, liver, synovial sarcoma, etc., with promising initial results. However, the potential benefit of using IGF-1R targeted therapy in pancreatic cancer is not fully explored. Further, there is still a lack of detailed knowledge regarding the exact molecular mechanisms by which IGF-1R regulates pancreatic carcinogenesis. Therefore, based on mounting evidence for the efficacy of targeting IGF-1R in a broad spectrum of cancers, we have determined the effects of targeting IGF-1R in pancreatic cancer in this study. The ultimate goal of this study is to identify whether IGF-1R signaling is an effective therapeutic target for pancreatic cancer with the potential to translate rapidly into clinical use. Here we clearly demonstrate that blocking IGF-1R expression enhances apoptosis and suppresses cell invasion, migration and metastasis via modulation of PI3K/AKT, MAPK and JAK/STAT signaling pathways in pancreatic cancer cells. , COX-2, pPTEN, pmTOR, mTOR, p-p70s6kinase and p70s6kinase ; Caspase8 ; b-actin. Appropriate secondary antibodies were obtained from Santa Cruz Biotechnology. Pancreas Adenocarcinoma Tissue Array Pancreas adenocarcinoma tissue microarray was obtained from US PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19655565 Biomax, Inc, Rockville, MD The TMA containing formalin-fixed paraffin embedded samples of pancreatic adenocarcinoma and normal pancreatic tissues was subjected to immunohistochemistry to determine IGF-1R expression levels. Institutional Review Board approval was not required for using TMAs. Immunohistochemistry IHC for IGF-1R antigen was performed using the pancreas adenocarcionma TMA. TMAs were first incubated in an oven at 58uC for 2 h to enhance tissue adhesion to the charged glass slides. Deparaffin
