PMID- 25915843
OWN - NLM
STAT- MEDLINE
DCOM- 20160620
LR  - 20190508
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 35
IP  - 4
DP  - 2016 Jan 28
TI  - An antibody to amphiregulin, an abundant growth factor in patients' fluids, 
      inhibits ovarian tumors.
PG  - 438-47
LID - 10.1038/onc.2015.93 [doi]
AB  - 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.
FAU - Carvalho, S
AU  - Carvalho S
AD  - Department of Biological Regulation, Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Lindzen, M
AU  - Lindzen M
AD  - Department of Biological Regulation, Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Lauriola, M
AU  - Lauriola M
AD  - Department of Biological Regulation, Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Shirazi, N
AU  - Shirazi N
AD  - Department of Biological Regulation, Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Sinha, S
AU  - Sinha S
AD  - Department of Biological Regulation, Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Abdul-Hai, A
AU  - Abdul-Hai A
AD  - Kaplan Medical Center, Rehovot, Israel.
FAU - Levanon, K
AU  - Levanon K
AD  - The Dr. Pinchas Borenstein Talpiot Medical Leadership Program and Institute of 
      Oncology, The Institute of Oncology, Chaim Sheba Medical Center, Ramat Gan, 
      Israel.
FAU - Korach, J
AU  - Korach J
AD  - Department of Gynecologic Oncology, Chaim Sheba Medical Center, Ramat Gan, 
      Israel.
FAU - Barshack, I
AU  - Barshack I
AD  - Department of Pathology, Sheba Medical Center, Ramat Gan, Israel.
FAU - Cohen, Y
AU  - Cohen Y
AD  - Institutional Tissue Banks, Sheba Medical Center, Ramat Gan, Israel.
FAU - Onn, A
AU  - Onn A
AD  - Institute of Pulmonary Oncology, Chaim Sheba Medical Center Ramat Gan, Israel.
FAU - Mills, G
AU  - Mills G
AD  - Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 
      Houston, TX, USA.
FAU - Yarden, Y
AU  - Yarden Y
AD  - Department of Biological Regulation, Weizmann Institute of Science, Rehovot, 
      Israel.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150427
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Transforming Growth Factor alpha)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Amphiregulin
MH  - Animals
MH  - Antibodies, Monoclonal/immunology/*pharmacology
MH  - Antineoplastic Agents/pharmacology
MH  - Culture Media, Conditioned/analysis
MH  - EGF Family of Proteins/*genetics/immunology/*metabolism
MH  - ErbB Receptors/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Mice, Nude
MH  - Molecular Targeted Therapy/methods
MH  - Ovarian Neoplasms/*drug therapy/genetics/*pathology
MH  - Transforming Growth Factor alpha/metabolism/pharmacology
MH  - Tumor Cells, Cultured
MH  - Ubiquitination
MH  - Xenograft Model Antitumor Assays
EDAT- 2015/04/29 06:00
MHDA- 2016/06/21 06:00
CRDT- 2015/04/28 06:00
PHST- 2014/10/12 00:00 [received]
PHST- 2015/02/26 00:00 [revised]
PHST- 2015/02/27 00:00 [accepted]
PHST- 2015/04/28 06:00 [entrez]
PHST- 2015/04/29 06:00 [pubmed]
PHST- 2016/06/21 06:00 [medline]
AID - onc201593 [pii]
AID - 10.1038/onc.2015.93 [doi]
PST - ppublish
SO  - Oncogene. 2016 Jan 28;35(4):438-47. doi: 10.1038/onc.2015.93. Epub 2015 Apr 27.