We found that down regulation of Notch 1 by small interfering RNA or, secretase inhibitors before TW 37 therapy triggered enhanced cell growth inhibition and apoptosis. Our data suggest that the observed ALK inhibitor anti-tumor action of TW 37i s mediated through a novel pathway involving inactivation of Notch 1 and Jagged 1. Pancreatic cancer remains among the most aggressive cancers using a very poor prognosis. A lot more than 33,000 patients die with this deadly disease each year in the United States. A large proportion of individuals present with gross metastases or micrometastases requiring effective drug therapies. But, traditional chemotherapy indicates only a small survival advantage when along with surgical resection. This result shows that new and alternative approaches to the get a handle on of cancer are critically needed. Pancreatic cancer is demonstrated to overexpress Bcl 2 and its family members. Consequently, blockade of Bcl 2 exercise must develop into a novel therapeutic strategy for pancreatic cancer. Several groups have been trying to develop anticancer drugs that block the function of Bcl 2 people. TW 37, a recently developed small molecule inhibitor of Bcl 2, targets Eumycetoma multiple members of the Bcl 2 family and attenuates activation of Bcl 2. TW 37 was built to target the piercing rhythm of anti-apoptotic proteins that usually bind the BH3 domain of proapoptotic effectors such as Bid, Bax, Bim, and others. We have found that TW 37 inhibits the development of various cancer cells, including chest, prostate, lymphoma, and pancreatic cancer. Nevertheless, the exact mechanism of action of TW 37 as an antitumor agent has not yet been fully established. It is well documented that Bcl 2 characteristics through heterodimerization with proapoptotic members of the Bcl 2 family to prevent mitochondrial pore formation and prevent cytochrome c release and initiation of apoptosis. But, you can find more Aurora B inhibitor evidences showing that Bcl 2 might play an oncogenic role through success pathways besides its function in the mitochondrial membrane. . It’s been reported that Bcl 2 activates nuclear factor nB by way of a signaling mechanism that involves Raf 1/MEKK 1 mediated activation of IKKh. Mortenson and colleagues show that overexpression of Bcl 2 increased the activity of IKK and AKT as well as NF nB transcriptional activity in pancreatic cancer. Kumar and colleagues found that Bcl 2 induced tumor cell invasion and tumor cell proliferation were significantly mediated by interleukin 8. Recently, Tucker and colleagues reported that Bcl 2 overexpression resulting in preservation of cyclin D1a expression may occur through p38 mitogen activated protein kinase mediated signaling pathways in human lymphoma cell lines. More over, down-regulation of Bcl 2 also could modulate the expression of anhydrase IX, vascular endothelial growth factor, and pAkt in prostate cancer cell lines.