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

20 Scopus citations

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    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, 35(4), 438-447. https://doi.org/10.1038/onc.2015.93