Ixabepilone Alone or With Cetuximab as First-Line Treatment for Advanced/Metastatic Triple-Negative Breast Cancer

Trédan, Olivier; Campone, Mario; Jassem, Jacek; Vyzula, Rostislav; Coudert, Bruno; Pacilio, Carmen; Prausová, Jana; Hardy-Bessard, Anne Claire; Arance, Ana; Mukhopadhyay, Pralay; Aloe, A.; Roché, Henri

doi:10.1016/j.clbc.2014.07.007

Cited by 52 publications

(37 citation statements)

References 36 publications

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“…While a tumor-promoting role of EGFR signaling in TNBC has been well established, the results of EGFR-targeted therapies for TNBC, either as a monotherapy or in combination with cisplatin, [49], carboplatin [50], or Ixabepilone [51], have been disappointing. One of the reasons is the lack of specific markers predicting which patients are most likely to respond to anti-EGFR therapies [1, 2, 52–55].…”

Section: Discussionmentioning

confidence: 99%

Metalloprotease-dependent activation of EGFR modulates CD44+/CD24− populations in triple negative breast cancer cells through the MEK/ERK pathway

Wise

Żółkiewska

2017

Breast Cancer Res Treat

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Purpose The CD44+/CD24− cell phenotype is enriched in triple negative breast cancers (TNBCs), is associated with tumor invasive properties, and serves as a cell surface marker profile of breast cancer stem-like cells. Activation of Epidermal Growth Factor Receptor (EGFR) promotes the CD44+/CD24− phenotype, but the specific signaling pathway downstream of EGFR responsible for this effect is not clear. The purpose of this study was to determine the role of the MEK/ERK pathway in the expansion of CD44+/CD24− populations in TNBC cells in response to EGFR activation. Methods Representative TNBC cell lines SUM159PT (claudin-low) and SUM149PT (basal) were used to evaluate cell surface expression of CD44 and CD24 by flow cytometry in response to EGFR and MEK inhibition or activation. EGFR and ERK phosphorylation levels were analyzed by Western blotting. The relationship between EGFR phosphorylation and MEK activation score in basal and claudin-low tumors from the TCGA database was examined. Results Inhibition of ERK activation with selumetinib, a MEK1/2 inhibitor, blocked EGF-induced expansion of CD44+/CD24− populations. Sustained activation of ERK by overexpression of constitutively active MEK1 was sufficient to expand CD44+/CD24− populations in cells in which EGFR activity was blocked by either erlotinib, an EGFR kinase inhibitor, or BB-94, a metalloprotease inhibitor that prevents generation of soluble EGFR ligands. In basal and claudin-low tumors from the TCGA database, there was a positive correlation between EGFR_pY1068 and MEK activation score in tumors without genomic loss of DUSP4, a negative regulator of ERK, but not in tumors harboring DUSP4 deletion. Conclusion Our results demonstrate that ERK activation is a key event in EGFR-dependent regulation of CD44+/CD24− populations. Furthermore, our findings highlight the role of ligand-mediated EGFR signaling in the control of MEK/ERK pathway output in TNBC tumors without DUSP4 loss.

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Section: Discussionmentioning

confidence: 99%

Metalloprotease-dependent activation of EGFR modulates CD44+/CD24− populations in triple negative breast cancer cells through the MEK/ERK pathway

Wise

Żółkiewska

2017

Breast Cancer Res Treat

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“…However, the efficacies of EGFR inhibitors for treating TNBCs in clinical trials are disappointing. 15,16 Therefore, it is important to develop novel strategies that target components of the EGFR signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Picrasidine G decreases viability of MDA-MB 468 EGFR-overexpressing triple-negative breast cancer cells through inhibition of EGFR/STAT3 signaling pathway

Yamashita

Kondo

Zhao

et al. 2017

Bioorganic & Medicinal Chemistry Letters

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“…Several clinical trials tried to target a particular receptor or pathway, including EGFR, in patients with metastatic TNBC but failed to demonstrate a significant benefit (43)(44)(45)(46)(47). The result of abnormal EGFR mediation in molecular dysfunction remains unresolved and could be responsible for the failure of these trials together with inadequate patient selection (44).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Evaluation of Epidermal Growth Factor Receptor (EGFR) Genotype and Phenotype Parameters in Triple-negative Breast Cancers

Levva

Kotoula

Kostopoulos

et al. 2017

CGP

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Ixabepilone Alone or With Cetuximab as First-Line Treatment for Advanced/Metastatic Triple-Negative Breast Cancer

Cited by 52 publications

References 36 publications

Metalloprotease-dependent activation of EGFR modulates CD44+/CD24− populations in triple negative breast cancer cells through the MEK/ERK pathway

Metalloprotease-dependent activation of EGFR modulates CD44+/CD24− populations in triple negative breast cancer cells through the MEK/ERK pathway

Picrasidine G decreases viability of MDA-MB 468 EGFR-overexpressing triple-negative breast cancer cells through inhibition of EGFR/STAT3 signaling pathway

Prognostic Evaluation of Epidermal Growth Factor Receptor (EGFR) Genotype and Phenotype Parameters in Triple-negative Breast Cancers

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