Therapeutic approaches to modulating Notch signaling: current challenges and future prospects.

Hypoxia, notch signalling, and prostate cancer. Nat Rev Urol (2013) 2.24

Notch signaling pathway targeted therapy suppresses tumor progression and metastatic spread in pancreatic cancer. Cancer Lett (2013) 1.22

Significance of glycosylation in Notch signaling. Biochem Biophys Res Commun (2014) 1.09

Structural analysis uncovers lipid-binding properties of Notch ligands. Cell Rep (2013) 1.06

Activation of nuclear PTEN by inhibition of Notch signaling induces G2/M cell cycle arrest in gastric cancer. Oncogene (2015) 0.97

Notch signaling in pancreatic cancer: oncogene or tumor suppressor? Trends Mol Med (2013) 0.95

The role of epithelial plasticity in prostate cancer dissemination and treatment resistance. Cancer Metastasis Rev (2014) 0.94

Emerging therapeutic biomarkers in endometrial cancer. Biomed Res Int (2013) 0.93

Expression profiling of stem cell-related genes in neoadjuvant-treated gastric cancer: a NOTCH2, GSK3B and β-catenin gene signature predicts survival. PLoS One (2012) 0.92

Protein trafficking abnormalities in Drosophila tissues with impaired activity of the ZIP7 zinc transporter Catsup. Development (2013) 0.92

Evolving understanding of the CLL genome. Semin Hematol (2014) 0.91

The truncate mutation of Notch2 enhances cell proliferation through activating the NF-κB signal pathway in the diffuse large B-cell lymphomas. PLoS One (2014) 0.90

Notch is a direct negative regulator of the DNA-damage response. Nat Struct Mol Biol (2015) 0.90

Sonic Hedgehog promotes proliferation of Notch-dependent monociliated choroid plexus tumour cells. Nat Cell Biol (2016) 0.87

Small molecules intercept Notch signaling and the early secretory pathway. Nat Chem Biol (2013) 0.83

NUMB inhibition of NOTCH signalling as a therapeutic target in prostate cancer. Nat Rev Urol (2014) 0.83

Structural and functional dissection of the interplay between lipid and Notch binding by human Notch ligands. EMBO J (2017) 0.82

Regulation of progenitor cell proliferation and neuronal differentiation in enteric nervous system neurospheres. PLoS One (2013) 0.82

Inhibition of Notch pathway attenuates the progression of human immunodeficiency virus-associated nephropathy. Am J Physiol Renal Physiol (2013) 0.80

Γ-secretase components as predictors of breast cancer outcome. PLoS One (2013) 0.80

The spectrum of genetic defects in chronic lymphocytic leukemia. Mediterr J Hematol Infect Dis (2012) 0.78

Notch-1 Confers Chemoresistance in Lung Adenocarcinoma to Taxanes through AP-1/microRNA-451 Mediated Regulation of MDR-1. Mol Ther Nucleic Acids (2016) 0.77

Notch signaling in pediatric soft tissue sarcomas. BMC Med (2012) 0.77

Prediabetic changes in gene expression induced by aspartame and monosodium glutamate in Trans fat-fed C57Bl/6 J mice. Nutr Metab (Lond) (2013) 0.77

An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth. J Exp Med (2016) 0.75

Concerning consequences of blocking Notch signaling in satellite muscle stem cells. Front Cell Dev Biol (2015) 0.75

Notch Signaling in T Helper Cell Subsets: Instructor or Unbiased Amplifier? Front Immunol (2017) 0.75

A Novel Assay for the Identification of NOTCH1 PEST Domain Mutations in Chronic Lymphocytic Leukemia. Biomed Res Int (2016) 0.75

Inhibition of γ-secretase activity synergistically enhances tumour necrosis factor-related apoptosis-inducing ligand induced apoptosis in T-cell acute lymphoblastic leukemia cells via upregulation of death receptor 5. Oncol Lett (2016) 0.75

Circulating-free DNA Mutation Associated with Response of Targeted Therapy in Human Epidermal Growth Factor Receptor 2-positive Metastatic Breast Cancer. Chin Med J (Engl) (2017) 0.75

Targeting the Notch signaling pathway in cancer therapeutics. Thorac Cancer (2014) 0.75

Neighbours of cancer-related proteins have key influence on pathogenesis and could increase the drug target space for anticancer therapies. NPJ Syst Biol Appl (2017) 0.75

Clinical utility of recently identified diagnostic, prognostic, and predictive molecular biomarkers in mature B-cell neoplasms. Mod Pathol (2017) 0.75

Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science (2004) 18.84

Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature (2005) 11.49

TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell (1991) 10.06

Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med (2007) 6.55

Direct inhibition of the NOTCH transcription factor complex. Nature (2009) 4.82

Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. EMBO J (2004) 4.77

High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res (2005) 4.61

FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. J Exp Med (2007) 4.59

Therapeutic antibody targeting of individual Notch receptors. Nature (2010) 4.56

Stem cells in normal breast development and breast cancer. Cell Prolif (2003) 4.47

Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem (2001) 4.45

Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signaling. Mol Cell Biol (2003) 4.43

Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem (2004) 4.27

The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov (2011) 4.24

Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells. Nat Med (2002) 4.04

Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia. Nat Med (2008) 3.98

Aberrant activation of notch signaling in human breast cancer. Cancer Res (2006) 3.92

Modulation of notch processing by gamma-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation. Toxicol Sci (2004) 3.85

Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res (2006) 3.81

DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency. Cell Stem Cell (2009) 3.48

Presenilin 1 is linked with gamma-secretase activity in the detergent solubilized state. Proc Natl Acad Sci U S A (2000) 3.13

Activating Notch1 mutations in mouse models of T-ALL. Blood (2005) 3.08

Rational targeting of Notch signaling in cancer. Oncogene (2008) 3.02

Leukemia-associated mutations within the NOTCH1 heterodimerization domain fall into at least two distinct mechanistic classes. Mol Cell Biol (2006) 2.94

Mastermind critically regulates Notch-mediated lymphoid cell fate decisions. Blood (2004) 2.90

Notch signaling induces cell cycle arrest in small cell lung cancer cells. Cancer Res (2001) 2.79

Anti-aβ therapeutics in Alzheimer's disease: the need for a paradigm shift. Neuron (2011) 2.67

Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands. Genes Dev (1992) 2.59

Gamma-secretase inhibitor prevents Notch3 activation and reduces proliferation in human lung cancers. Cancer Res (2007) 2.54

Chromosome 19 translocation, overexpression of Notch3, and human lung cancer. J Natl Cancer Inst (2000) 2.45

Involvement of Notch-1 signaling in bone marrow stroma-mediated de novo drug resistance of myeloma and other malignant lymphoid cell lines. Blood (2003) 2.41

CUTLL1, a novel human T-cell lymphoma cell line with t(7;9) rearrangement, aberrant NOTCH1 activation and high sensitivity to gamma-secretase inhibitors. Leukemia (2006) 2.40

Presenilin-1 and -2 are molecular targets for gamma-secretase inhibitors. J Biol Chem (2000) 2.33

Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional gamma-secretase inhibitor. J Biol Chem (2003) 2.22

Inhibition of gamma-secretase activity inhibits tumor progression in a mouse model of pancreatic ductal adenocarcinoma. Gastroenterology (2009) 2.17

Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma. Blood (2002) 2.03

Apoptosis in T cell acute lymphoblastic leukemia cells after cell cycle arrest induced by pharmacological inhibition of notch signaling. Chem Biol (2007) 2.02

Conservation of the Drosophila lateral inhibition pathway in human lung cancer: a hairy-related protein (HES-1) directly represses achaete-scute homolog-1 expression. Proc Natl Acad Sci U S A (1997) 2.00

Involvement of Notch1 in the development of mouse mammary tumors. Oncogene (1999) 1.99

gamma-Secretase inhibitors abrogate oxaliplatin-induced activation of the Notch-1 signaling pathway in colon cancer cells resulting in enhanced chemosensitivity. Cancer Res (2009) 1.98

Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies. Blood (2005) 1.96

The possible correlation of Notch-1 and Notch-2 with clinical outcome and tumour clinicopathological parameters in human breast cancer. Int J Mol Med (2004) 1.86

NOTCH1 extracellular juxtamembrane expansion mutations in T-ALL. Blood (2008) 1.84

Modulation of Notch signaling by antibodies specific for the extracellular negative regulatory region of NOTCH3. J Biol Chem (2008) 1.83

The mouse mammary tumor associated gene INT3 is a unique member of the NOTCH gene family (NOTCH4). Oncogene (1997) 1.81

A notch1 ectodomain construct inhibits endothelial notch signaling, tumor growth, and angiogenesis. Cancer Res (2008) 1.80

Notch in lung development and lung cancer. Semin Cancer Biol (2004) 1.73

ErbB-2 inhibition activates Notch-1 and sensitizes breast cancer cells to a gamma-secretase inhibitor. Oncogene (2008) 1.69

In vitro validation of gamma-secretase inhibitors alone or in combination with other anti-cancer drugs for the treatment of T-cell acute lymphoblastic leukemia. Haematologica (2008) 1.69

Notch-induced T cell development requires phosphoinositide-dependent kinase 1. EMBO J (2007) 1.67

Inhibition of Notch signaling induces apoptosis of myeloma cells and enhances sensitivity to chemotherapy. Blood (2007) 1.65

Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi's sarcoma tumor cells. Oncogene (2005) 1.63

Evaluation of selective gamma-secretase inhibitor PF-03084014 for its antitumor efficacy and gastrointestinal safety to guide optimal clinical trial design. Mol Cancer Ther (2010) 1.62

Modulation of notch signaling elicits signature tumors and inhibits hras1-induced oncogenesis in the mouse mammary epithelium. Am J Pathol (2004) 1.59

Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. Cancer Res (2009) 1.58

Establishment of a novel B-cell lymphoma cell line with suppressed growth by gamma-secretase inhibitors. Leuk Res (2006) 1.57

Cell cycle arrest and apoptosis induced by Notch1 in B cells. J Biol Chem (2000) 1.45

Notch-1 mutations are secondary events in some patients with T-cell acute lymphoblastic leukemia. Clin Cancer Res (2007) 1.44

Constitutive activation of Notch3 inhibits terminal epithelial differentiation in lungs of transgenic mice. Oncogene (2003) 1.44

Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells. Blood (2004) 1.43

Characterization of Notch1 antibodies that inhibit signaling of both normal and mutated Notch1 receptors. PLoS One (2010) 1.41

Notch activation induces Akt signaling via an autocrine loop to prevent apoptosis in breast epithelial cells. Cancer Res (2009) 1.40

Phase I trial of MK-0752 in children with refractory CNS malignancies: a pediatric brain tumor consortium study. J Clin Oncol (2011) 1.39

Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines. Blood (2004) 1.38

Anti-DLL4 inhibits growth and reduces tumor-initiating cell frequency in colorectal tumors with oncogenic KRAS mutations. Cancer Res (2010) 1.32

Notch2 is involved in the overexpression of CD23 in B-cell chronic lymphocytic leukemia. Blood (2002) 1.31

A substrate-based difluoro ketone selectively inhibits Alzheimer's gamma-secretase activity. J Med Chem (1998) 1.25

Concentration-dependent modulation of amyloid-beta in vivo and in vitro using the gamma-secretase inhibitor, LY-450139. J Pharmacol Exp Ther (2006) 1.25

JAGGED1 and delta1 differentially regulate the outcome of experimental autoimmune encephalomyelitis. J Immunol (2007) 1.23

Identification of a novel NOTCH-4/INT-3 RNA species encoding an activated gene product in certain human tumor cell lines. Oncogene (2000) 1.23

Targeting both Notch and ErbB-2 signalling pathways is required for prevention of ErbB-2-positive breast tumour recurrence. Br J Cancer (2011) 1.23

The cytotoxicity of gamma-secretase inhibitor I to breast cancer cells is mediated by proteasome inhibition, not by gamma-secretase inhibition. Breast Cancer Res (2009) 1.19

Downregulation of Notch pathway by a gamma-secretase inhibitor attenuates AKT/mammalian target of rapamycin signaling and glucose uptake in an ERBB2 transgenic breast cancer model. Cancer Res (2010) 1.19

Structure and function of gamma-secretase. Semin Cell Dev Biol (2008) 1.19

Targeting notch pathway enhances rapamycin antitumor activity in pancreas cancers through PTEN phosphorylation. Mol Cancer (2011) 1.17

γ-Secretase inhibitors and modulators for Alzheimer's disease. J Neurochem (2011) 1.09

Targeting ADAM-17/notch signaling abrogates the development of systemic sclerosis in a murine model. Arthritis Rheum (2010) 1.05

ADAM10 as a target for anti-cancer therapy. Curr Pharm Biotechnol (2008) 1.04

Down-regulation of the Notch pathway mediated by a gamma-secretase inhibitor induces anti-tumour effects in mouse models of T-cell leukaemia. Br J Pharmacol (2009) 1.04

Neutralization of the γ-secretase activity by monoclonal antibody against extracellular domain of nicastrin. Oncogene (2011) 1.03

Notch inhibition blocks multiple myeloma cell-induced osteoclast activation. Leukemia (2008) 0.99

Notch signaling proteins: legitimate targets for cancer therapy. Curr Protein Pept Sci (2010) 0.98

Pharmacodynamics and pharmacokinetics of the gamma-secretase inhibitor PF-3084014. J Pharmacol Exp Ther (2010) 0.97

Gamma-secretase inhibitors suppress the growth of leukemia and lymphoma cells. Oncol Rep (2007) 0.97

Combined inhibition of Notch signaling and Bcl-2/Bcl-xL results in synergistic antimyeloma effect. Mol Cancer Ther (2010) 0.93

Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase. J Med Chem (2004) 0.93

Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a γ-secretase inhibitor targeting notch signaling. Pediatr Blood Cancer (2011) 0.91

Inhibition of gamma-secretase affects proliferation of leukemia and hepatoma cell lines through Notch signaling. Anticancer Drugs (2008) 0.90

Gamma-secretase inhibitor enhances the cytotoxic effect of bortezomib in multiple myeloma. Cell Oncol (Dordr) (2011) 0.87

Notch1 enhances B-cell receptor-induced apoptosis in mature activated B cells without affecting cell cycle progression and surface IgM expression. Cell Death Differ (2003) 0.85

GSI-I (Z-LLNle-CHO) inhibits γ-secretase and the proteosome to trigger cell death in precursor-B acute lymphoblastic leukemia. Leukemia (2011) 0.82

Endosomal entry regulates Notch receptor activation in Drosophila melanogaster. J Cell Biol (2008) 2.32

Human neurodegenerative disease modeling using Drosophila. Annu Rev Neurosci (2003) 1.53

Nicastrin is required for gamma-secretase cleavage of the Drosophila Notch receptor. Dev Cell (2002) 1.40

Different cofactor activities in gamma-secretase assembly: evidence for a nicastrin-Aph-1 subcomplex. J Cell Biol (2003) 1.38

Retracted The big brain aquaporin is required for endosome maturation and notch receptor trafficking. Cell (2008) 0.98

Modeling clinically heterogeneous presenilin mutations with transgenic Drosophila. Curr Biol (2006) 0.97

Functional reconstitution of gamma-secretase through coordinated expression of presenilin, nicastrin, Aph-1, and Pen-2. J Neurosci Res (2004) 0.93

Protein trafficking abnormalities in Drosophila tissues with impaired activity of the ZIP7 zinc transporter Catsup. Development (2013) 0.92

Notch signaling: a different sort makes the cut. Curr Biol (2004) 0.91

Introduction--Notch in development and disease. Semin Cell Dev Biol (2012) 0.84

In vivo reconstitution of gamma-secretase in Drosophila results in substrate specificity. Mol Cell Biol (2010) 0.83

Neurobiology: double trouble for neurons. Nature (2003) 0.83

Pharmacological and genetic reversal of age-dependent cognitive deficits attributable to decreased presenilin function. J Neurosci (2010) 0.82

Deficient Notch signaling associated with neurogenic pecanex is compensated for by the unfolded protein response in Drosophila. Development (2011) 0.81

Pharmacological analysis of Drosophila melanogaster gamma-secretase with respect to differential proteolysis of Notch and APP. Mol Pharmacol (2010) 0.81

A role for presenilin in post-stress regulation: effects of presenilin mutations on Ca2+ currents in Drosophila. FASEB J (2007) 0.78

Disruption of Drosophila melanogaster lipid metabolism genes causes tissue overgrowth associated with altered developmental signaling. PLoS Genet (2013) 0.78

Inheritance of susceptibility to induction of nephroblastomas in the Noble rat. Differentiation (2009) 0.77

Drosophila as a model for human diseases: IRB and ICREA, Barcelona, Spain, October 5-7, 2006. Fly (Austin) (2007) 0.76

Retracted gamma-cleavage-independent functions of presenilin, nicastrin, and Aph-1 regulate cell-junction organization and prevent tau toxicity in vivo. Neuron (2006) 0.76

Generation and characterization of monoclonal antibodies specific to Drosophila presenilin. Hybridoma (Larchmt) (2009) 0.75

Transcriptomic Analysis of Drosophila Mushroom Body Neurons Lacking Amyloid-β Precursor-Like Protein Activity. J Alzheimers Dis (2015) 0.75

Applications of the Drosophila retina to human disease modeling. Results Probl Cell Differ (2002) 0.75

gamma-cleavage-independent functions of presenilin, nicastrin, and Aph-1 regulate cell-junction organization and prevent tau toxicity in vivo. Neuron (2007) 0.75