Rational targeting of Notch signaling in cancer

Rizzo, Paola; Osipo, Clodia; Foreman, Kimberly E.; Golde, Todd E.; Osborne, B; Miele, Lucio

doi:10.1038/onc.2008.226

Cited by 364 publications

(324 citation statements)

References 74 publications

Supporting

Mentioning

315

Contrasting

Unclassified

Order By: Relevance

“…[69][70][71], inhibiting a signaling pathway predominantly activated in the CSCs (e.g., Notch, Wnt etc.) [72,73], immunomodulation (e.g., CD326, ALDH1 inhibitor) [73,74], sensitizing CSCs to systemic chemotherapy/radiation (e.g., IL4, hyaluronate receptor) [56,75] or inhibiting CSC angiogenesis (e.g., VEGF-R, DLL4) [76][77][78]. An important contribution of CSC research to anti-cancer targeted treatment is that it unveils specific biomarkers which can be targeted in vivo by antibody therapy leading to disrupted tumor growth [60,67,79,80].…”

Section: Targeted Therapy-targeting Cscs In Wtmentioning

confidence: 99%

Targeted therapy aimed at cancer stem cells: Wilms’ tumor as an example

2013

View full text Add to dashboard Cite

Wilms' tumor (WT), a common renal pediatric solid tumor, serves as a model for a malignancy formed by renal precursor cells that have failed to differentiate properly. Here we review recent evidence showing that the tumors' heterogeneous cell population contains a small fraction of cancer stem cells (CSC) identified by two markers: Neural Cell Adhesion Molecule 1 (NCAM1) expression and Aldehyde dehydrogenase 1 (ALDH1) enzymatic activity. In vivo studies show these CSCs to both self-renew and differentiate to give rise to all tumor components. Similar to other malignancies, the identification of a specific CSC fraction has allowed the examination of a novel targeted therapy, aimed at eradicating the CSC population. The loss of CSCs abolishes the tumor's ability to sustain and propagate, hence, causing tumor degradation with minimal damage to normal tissue.

show abstract

Section: Targeted Therapy-targeting Cscs In Wtmentioning

confidence: 99%

Targeted therapy aimed at cancer stem cells: Wilms’ tumor as an example

2013

View full text Add to dashboard Cite

show abstract

“…The MDA-MB-468 line expresses Notch 1 (Stylianou et al, 2006) and Notch 3 (Yamaguchi et al, 2008). The MCF-7 line expresses Notch 1 (Stylianou et al, 2006;Rizzo et al, 2008), Notch 3 (Yamaguchi et al, 2008) and Notch 4 (Sun et al, 2005). However, Notch 3 selectively dominates in MARY-X.…”

Section: Notch 3 Dependency Of Ibc Embolus Y Xiao Et Almentioning

confidence: 99%

The lymphovascular embolus of inflammatory breast cancer exhibits a Notch 3 addiction

Xiao

Zou

et al. 2010

Oncogene

View full text Add to dashboard Cite

“…Several studies suggest that Notch receptor and ligands are overexpressed in the breast cancer tissues compared with the normal breast epithelium (14,27,43,44) and there is a strong correlation between high expression of Notch1 and Jagged1 and poor prognosis and survival (15). Because mAb 602.101 inhibited Jagged1 and Delta-like4 activities in the Notch1-overexpressing cells, ability of this antibody to inhibit Notch signaling in the cancer cell lines MCF-7 and MDA-MB-231 was investigated.…”

Section: Inhibition Of Notch Signaling In Breast Cancer Cell Lines Bymentioning

confidence: 99%

“…24,25). However, GSIs being universal inhibitors of g-secretases also inhibit other signaling pathways (26) and have limited therapeutic potential because of their serious adverse effects (27,28). Therefore, it is essential to generate tools that can exclusively target Notch signaling pathway and specific antibodies are the ideal molecules.…”

Section: Introductionmentioning

confidence: 99%

A Monoclonal Antibody against Human Notch1 Ligand–Binding Domain Depletes Subpopulation of Putative Breast Cancer Stem–like Cells

Sharma

Paranjape

Rangarajan

et al. 2012

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Overexpression of Notch receptors and ligands has been associated with various cancers and developmental disorders, making Notch a potential therapeutic target. Here, we report characterization of Notch1 monoclonal antibodies (mAb) with therapeutic potential. The mAbs generated against epidermal growth factor (EGF) repeats 11 to 15 inhibited binding of Jagged1 and Delta-like4 and consequently, signaling in a dose-dependent manner, the antibodies against EGF repeats 11 to 12 being more effective than those against repeats 13 to 15. These data emphasize the role of EGF repeats 11 to 12 in ligand binding. One of the mAbs, 602.101, which specifically recognizes Notch1, inhibited ligand-dependent expression of downstream target genes of Notch such as HES-1, HES-5, and HEY-L in the breast cancer cell line MDA-MB-231. The mAb also decreased cell proliferation and induced apoptotic cell death. Furthermore, exposure to this antibody reduced CD44 Hi / CD24 Low subpopulation in MDA-MB-231 cells, suggesting a decrease in the cancer stem-like cell subpopulation. This was confirmed by showing that exposure to the antibody decreased the primary, secondary, and tertiary mammosphere formation efficiency of the cells. Interestingly, effect of the antibody on the putative stem-like cells appeared to be irreversible, because the mammosphere-forming efficiency could not be salvaged even after antibody removal during the secondary sphere formation. The antibody also modulated expression of genes associated with stemness and epithelial-mesenchymal transition. Thus, targeting individual Notch receptors by specific mAbs is a potential therapeutic strategy to reduce the potential breast cancer stem-like cell subpopulation.

show abstract

Rational targeting of Notch signaling in cancer

Cited by 364 publications

References 74 publications

Targeted therapy aimed at cancer stem cells: Wilms’ tumor as an example

Targeted therapy aimed at cancer stem cells: Wilms’ tumor as an example

The lymphovascular embolus of inflammatory breast cancer exhibits a Notch 3 addiction

A Monoclonal Antibody against Human Notch1 Ligand–Binding Domain Depletes Subpopulation of Putative Breast Cancer Stem–like Cells

Contact Info

Product

Resources

About