En effects of Notch-targeting therapies Therapy GSIs DAPT GSI, unspecified DAPT MRK-003, GSI-18 DAPT Tissue AML-derived stem cells Tal1/Lmo2 mouse model of T-ALL Breast cancer cell lines Glioma cell line neurospheres Main GBM explant cultures Effect Inhibition of colony formation Decreased or eliminated CSCs; improved survival of animals Lowered variety of putative breast CSCs Reduced clonogenicity; dose-dependent reduction in CSC markers; prolonged survival; reduced tumor-forming potential Combination of Notch inhibition and radiation drastically decreased proliferation and self-renewal in tumor explants compared with radiation therapy alone Lowered putative CSC population; decreased proliferation and elevated differentiation; induced apoptosis in nestin-positive cells; inhibited engraftment in vivo Sensitized cells to cisplatin treatment Sensitized cells to chemotherapy; synergistic with oxaliplatin, 5-FU and SN-38 Mixture with TMZ prevented recovery of neurospheres compared with recovery in posttreatment period with TMZ treatment alone In mixture with TMZ-blocked tumor progression in 50 of mice Rendered glioma CSCs far more sensitive to radiation, enhanced radiation-induced cell death and impaired clonogenic survival Inhibition of anchorage-independent growth; lowered number of CSCs; pretreatment of xenograph inhibited engraftment in mice; blocked xenograph development in 56 of mice Inhibited survival of tumorsphere-derived cells in vitro; reduced or eliminated CSCs as assessed by failure of serial transplantation; administration to tumor-bearing mice resulted in rapid and lasting tumor regression Growth inhibition of autochthonous murine tumors; greater frequency of apoptosis in drug-treated versus vehicle-treated cells; mice treated with GSI showed total blockade of cancer growth Inhibition of tumor growth by means of inhibition of cancer cell development without GI toxicity Induced differentiation of neural stem cells into neuronal cells Blocked tumor growth by promoting non-productive angiogenesis Reference 80 81 85 91GSI-MedulloblastomaGSI1 GSI34 DAPT LY411,575 DAPT, L685,458 MRK-Ovarian cancer cell lines Colon cancer cell lines Glioma cell lines Glioma xenograph in mice Glioma surgical specimen CSCs Pancreatic ductal adenocarcinoma cell lines and patient-derived xenographs Mouse model of ERBB2 breast cancer recognized to possess a high CSC frequency KrasG12V-driven NSCLC109 111 112 112 113MRK-LSN-Antibodies targeting Notch pathway proteins Distinct anti-Notch1 antibody Xenograph lung cancer and melanoma cell lines Mixture of specific Human neuroepithelial stem cells anti-Notch1, anti-Notch-2 and anti-Notch-3 antibodies Anti-DLL-4 antibody Human umbilical vein endothelial cells alone (unspecified) and cocultured with glioma cells, DLL-4 reporter mice with xenograph tumors Anti-DLL-4 antibody MEDI0639 Human umbilical vein endothelial cells Anti-DLL-4 antibody (unspecified) DLL-4+ and DLL-4- tumor xenographs128 129Reduced quantity of functional vessels as measured by 132 variety of actin-positive smooth-muscle mural cells Fourfold reduction in tumor development rate when treated with 134 antibody and ionizing radiation in comparison with GSI dibenzazepine and ionizing radiationineffective drug.Panitumumab At present, many groups are operating to refine both our understanding of your mechanisms by which the Notch pathway increases the malignant phenotype and our capability to regulate Notch signaling so that you can develop novel therapeutic tactics targeting.Docetaxel PMID:24605203