An antibody to amphiregulin, an abundant growth factor in patients' fluids, inhibits ovarian tumors

S. Carvalho, M. Lindzen, M. Lauriola, N. Shirazi, S. Sinha, A. Abdul-Hai, K. Levanon, J. Korach, I. Barshack, Y. Cohen, A. Onn, Gordon Mills, Y. Yarden

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Growth factors of the epidermal growth factor (EGF)/neuregulin family are involved in tumor progression and, accordingly, antibodies that intercept a cognate receptor, epidermal growth factor receptor (EGFR)/ERBB1, or a co-receptor, HER2, have been approved for cancer therapy. Although they might improve safety and delay onset of chemoresistance, no anti-ligand antibodies have been clinically approved. To identify suitable ligands, we surveyed fluids from ovarian and lung cancer patients and found that amphiregulin (AREG) is the most abundant and generalized ligand secreted by advanced tumors. AREG is a low affinity EGFR ligand, which is upregulated following treatment with chemotherapeutic drugs. Because AREG depletion retarded growth of xenografted ovarian tumors in mice, we generated a neutralizing monoclonal anti-AREG antibody. The antibody inhibited growth of ovarian cancer xenografts and strongly enhanced chemotherapy efficacy. Taken together, these results raise the possibility that AREG and other low- or high-affinity binders of EGFR might serve as potential targets for cancer therapy.

Original languageEnglish (US)
Pages (from-to)438-447
Number of pages10
JournalOncogene
Volume35
Issue number4
DOIs
StatePublished - Jan 28 2016
Externally publishedYes

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Intercellular Signaling Peptides and Proteins
Epidermal Growth Factor Receptor
Antibodies
Ligands
Neoplasms
Ovarian Neoplasms
Anti-Idiotypic Antibodies
Neuregulins
Growth
Epidermal Growth Factor
Heterografts
Lung Neoplasms
Therapeutics
Monoclonal Antibodies
Amphiregulin
Safety
Drug Therapy
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Carvalho, S., Lindzen, M., Lauriola, M., Shirazi, N., Sinha, S., Abdul-Hai, A., ... Yarden, Y. (2016). An antibody to amphiregulin, an abundant growth factor in patients' fluids, inhibits ovarian tumors. Oncogene, 35(4), 438-447. https://doi.org/10.1038/onc.2015.93

An antibody to amphiregulin, an abundant growth factor in patients' fluids, inhibits ovarian tumors. / Carvalho, S.; Lindzen, M.; Lauriola, M.; Shirazi, N.; Sinha, S.; Abdul-Hai, A.; Levanon, K.; Korach, J.; Barshack, I.; Cohen, Y.; Onn, A.; Mills, Gordon; Yarden, Y.

In: Oncogene, Vol. 35, No. 4, 28.01.2016, p. 438-447.

Research output: Contribution to journalArticle

Carvalho, S, Lindzen, M, Lauriola, M, Shirazi, N, Sinha, S, Abdul-Hai, A, Levanon, K, Korach, J, Barshack, I, Cohen, Y, Onn, A, Mills, G & Yarden, Y 2016, 'An antibody to amphiregulin, an abundant growth factor in patients' fluids, inhibits ovarian tumors', Oncogene, vol. 35, no. 4, pp. 438-447. https://doi.org/10.1038/onc.2015.93
Carvalho S, Lindzen M, Lauriola M, Shirazi N, Sinha S, Abdul-Hai A et al. An antibody to amphiregulin, an abundant growth factor in patients' fluids, inhibits ovarian tumors. Oncogene. 2016 Jan 28;35(4):438-447. https://doi.org/10.1038/onc.2015.93
Carvalho, S. ; Lindzen, M. ; Lauriola, M. ; Shirazi, N. ; Sinha, S. ; Abdul-Hai, A. ; Levanon, K. ; Korach, J. ; Barshack, I. ; Cohen, Y. ; Onn, A. ; Mills, Gordon ; Yarden, Y. / An antibody to amphiregulin, an abundant growth factor in patients' fluids, inhibits ovarian tumors. In: Oncogene. 2016 ; Vol. 35, No. 4. pp. 438-447.
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