Specific inhibition of Notch1 signaling enhances the antitumor efficacy of chemotherapy in triple negative breast cancer through reduction of cancer stem cells

Qiu, Ming; Peng, Qinghai; Jiang, Ivy; Carroll, Christopher L.; Han, Guangzhou; Rymer, Isha; Lippincott, John; Zachwieja, Joseph; Gajiwala, K.S.; Kraynov, Eugenia; Thibault, Stéphane; Stone, Donald S.; Gao, Yuanfeng; Sofia, Susan; Gallo, Jorge D.; Li, Gang; Yang, Jennifer; Li, Kang; Wei, Ping

doi:10.1016/j.canlet.2012.09.023

Cited by 126 publications

(104 citation statements)

References 42 publications

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“…Anti-Notch1 monoclonal antibodies can delay tumor recurrence and enhance the antitumor efficacy of chemotherapy (Qiu et al, 2013). The authors of previous studies have reported that expression of Notch1 is associated with a prognosis of breast cancer Yao et al, 2011;Zhu et al, 2013;Cao et al, 2014;Yuan et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…The forced expression of EZH2 in cell lines can increase proliferation and oncogenic capacity (Piunti and Pasini, 2011). Additionally, reducing EZH2 expression and EZH2 degradation inhibits cell growth and reduces tumor formation in cancers (Qiu et al, 2013). Ntziachristos et al (2012) reported that Notch1 interacts with EZH2 to control gene expression and cell transformation in T-cell acute lymphoblastic leukemia.…”

Section: Discussionmentioning

confidence: 99%

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Relationship between the expression of Notch1 and EZH2 and the prognosis of breast invasive ductal carcinoma

Zhao

Luan

et al. 2016

Genet. Mol. Res.

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ABSTRACT. We determined whether the coexpression of Notch1 and EZH2 influences the progression and prognosis of breast invasive ductal carcinoma. Using the c 2 test, a significant difference was found between high and low expression of Notch1 in terms of lymph node, hormone receptor, and p53 expression (P < 0.05). Moreover, a significant difference was found between high and low expression of EZH2 in terms of tumor size, histologic grade, hormone receptor, and expression of Ki67 (P < 0.05). Using Pearson correlation analysis, we found a significant positive correlation between Notch1 and EZH2 expression in the tissue samples of breast invasive ductal carcinoma (P = 0.038). High Notch1 and EZH2 expression was associated with poor progression-free survival compared with low expression (P Notch1 = 0.000, 40.3 vs 48.9 months; P EZH2 = 0.000, 40.2 vs 49.9 months). Moreover, we found that high Notch1 and EZH2 expression was associated with poor overall survival compared with low expression (P Notch1 = 0.000, 51.2 vs 56.2 months; P EZH2 = 0.002, 51.7 vs 56.4 months). In conclusion, Notch1 and EZH2 coexpression contributes to the progression and prognosis of breast invasive ductal carcinoma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Relationship between the expression of Notch1 and EZH2 and the prognosis of breast invasive ductal carcinoma

Zhao

Luan

et al. 2016

Genet. Mol. Res.

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“…ability of CSCs and tumor growth inhibition in xenograft models derived from triple negative breast cancer (TNBC) Sum149 cell line and TNBC patient primary cancer cells and has synergistic effect with docetaxel. 96 Moreover, Notch1 mAbs also resultes in decreased tumor incidence upon re-implantation and a delay in tumor recurrence of the TNBC cells. TNBC is very aggressive and currently there is no specific therapeutic stratge,inhibition of self-renewal pathway by Notch1 mAbs may provide a novel anticancer therapy on TNBC.…”

Section: Disclosure Of Potential Conflicts Of Interestmentioning

confidence: 99%

Therapeutic strategies targeting cancer stem cells

Ning

Shu

et al. 2013

Cancer Biology & Therapy

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“…Studies in conditional knockout mice have suggested that goblet cell metaplasia requires inhibition of both Notch1 and Notch2 receptors (48). Therefore, much effort has gone into the development of antibodies that specifically target various epitopes of Notch1 (20,21,27,49,50), with the expectation that this would eliminate gut toxicity. Surprisingly, however, it was reported that treatment of mice with antibodies that target Notch1 through binding to the negative regulatory region (NRR) can induce some level of goblet cell metaplasia (27).…”

Section: Discussionmentioning

confidence: 99%

“…Cancer stem cell maintenance is another area where Notch signaling is thought to play a key role (18,19). Inhibition of Notch1 in mouse models can reduce cancer stem cell numbers in both hematopoietic and solid tumors, potentially decreasing resistance to chemotherapy and delaying tumor recurrence (20)(21)(22). Finally, Notch1 activity in the microenvironment keeps VEGF signaling in check to optimize tumor angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

23814, an Inhibitory Antibody of Ligand-Mediated Notch1 Activation, Modulates Angiogenesis and Inhibits Tumor Growth without Gastrointestinal Toxicity

Proia

Jiang

Bell

et al. 2015

Molecular Cancer Therapeutics

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Dysregulation of Notch signaling has been implicated in the development of many different types of cancer. Notch inhibitors are being tested in the clinic, but in most cases gastrointestinal and other toxicities have limited the dosage and, therefore, the effectiveness of these therapies. Herein, we describe the generation of a monoclonal antibody against the ligand-binding domain of the Notch1 receptor that specifically blocks ligand-induced activation. This antibody, 23814, recognizes both human and murine Notch1 with similar affinity, enabling examination of the effects on both tumor and host tissue in preclinical models. 23814 blocked Notch1 function in vivo, inhibited functional angiogenesis, and inhibited tumor growth without causing gastrointestinal toxicity. The lack of toxicity allowed for combination of 23814 and the VEGFR inhibitor tivozanib, resulting in significant growth inhibition of several VEGFR inhibitor-resistant tumor models. Analysis of the gene expression profiles of an extensive collection of murine breast tumors enabled the successful prediction of which tumors were most likely to respond to the combination of 23814 and tivozanib. Therefore, the use of a specific Notch1 antibody that does not induce significant toxicity may allow combination treatment with angiogenesis inhibitors or other targeted agents to achieve enhanced therapeutic benefit. Mol Cancer Ther; 14(8); 1858–67. ©2015 AACR.

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Specific inhibition of Notch1 signaling enhances the antitumor efficacy of chemotherapy in triple negative breast cancer through reduction of cancer stem cells

Cited by 126 publications

References 42 publications

Relationship between the expression of Notch1 and EZH2 and the prognosis of breast invasive ductal carcinoma

Relationship between the expression of Notch1 and EZH2 and the prognosis of breast invasive ductal carcinoma

Therapeutic strategies targeting cancer stem cells

23814, an Inhibitory Antibody of Ligand-Mediated Notch1 Activation, Modulates Angiogenesis and Inhibits Tumor Growth without Gastrointestinal Toxicity

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