ErbB-3 Predicts Survival in Ovarian Cancer

Berno, Tamara; Hasenclever, Dirk; Stern, Katja; Schormann, Wiebke; Bezler, Martin; Hermes, Matthias; Brulport, Marc; Bauer, Alexander; Schiffer, Ilka B.; Gebhard, Susanne; Schmidt, M; Steiner, Eric; Sehouli, Jalid; Edelmann, Jeanett; Läuter, Jürgen; Lessig, Rüdiger; Krishnamurthi, Kannan; Ullrich, Axel; Hengstler, Jan G.

doi:10.1200/jco.2005.04.8397

Cited by 191 publications

(136 citation statements)

References 33 publications

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“…237 It has recently been confirmed that high ERBB3 expression in ovarian cancer correlates with poor survival. 246 In the latter immuno-histochemical study, ERBB3 overexpression was more common than high ERBB2 and the predominant localization of the ERBB3 protein was cytoplasmic, in contrast to the typical membrane staining for ERBB2.…”

Section: Ovarian Cancermentioning

confidence: 82%

The ERBB3 receptor in cancer and cancer gene therapy

2008

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ERBB3, a member of the epidermal growth factor receptor (EGFR) family, is unique in that its tyrosine kinase domain is functionally defective. It is activated by neuregulins, by other ERBB and nonERBB receptors as well as by other kinases, and by novel mechanisms. Downstream it interacts prominently with the phosphoinositol 3-kinase/AKT survival/mitogenic pathway, but also with GRB, SHC, SRC, ABL, rasGAP, SYK and the transcription regulator EBP1. There are likely important but poorly understood roles for nuclear localization and for secreted isoforms. Studies of ERBB3 expression in primary cancers and of its mechanistic contributions in cultured cells have implicated it, with varying degrees of certainty, with causation or sustenance of cancers of the breast, ovary, prostate, certain brain cells, retina, melanocytes, colon, pancreas, stomach, oral cavity and lung. Recent results link high ERBB3 activity with escape from therapy targeting other ERBBs in lung and breast cancers. Thus a wide and centrally important role for ERBB3 in cancer is becoming increasingly apparent. Several approaches for targeting ERBB3 in cancers have been tested or proposed. Small inhibitory RNA (siRNA) to ERBB3 or AKT is showing promise as a therapeutic approach to treatment of lung adenocarcinoma.

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Section: Ovarian Cancermentioning

confidence: 82%

The ERBB3 receptor in cancer and cancer gene therapy

2008

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“…Furthermore, only few studies have described the tissue expression of the HER3 and HER4 receptor protein in ovarian cancer. The HER3 receptor is present in the majority of malignant ovarian tumors (10)(11)(12)(13) and one study (14) has also reported that high HER3 expression is a poor prognostic factor in ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors

Steffensen¹,

Waldstrøm²,

Andersen³

et al. 2008

Int J Oncol

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“…ErbB-3 is highly expressed in many human tumor types and has been variably associated with poor prognosis (Yi et al, 1997;Tanner et al, 2006;Reschke et al, 2008). Moreover, recent studies suggest that breast cancers exposed to ErbB-1 or ErbB-2 targeted therapies escape this inhibition by persistent activation of ErbB-3 and the PI3-K-Akt pathways (Baselga and Swain 2009), suggesting that agents targeting ErbB-3 could provide a novel and promising approach toward the treatment of some cancers.…”

Section: Discussionmentioning

confidence: 99%

“…This resistance is often associated with compensation by or upregulation of other ErbB family members such as ErbB-3 and ErbB-4 (Bianchi et al, 2006;Engelman et al, 2007;Karamouzis et al, 2007) or increased production of ErbB-1 or ErbB-3 ligands by tumor cells (Ishikawa et al, 2005;Zhou et al, 2006). ErbB-3 overexpression has been documented in breast, ovarian and lung cancer and this genetic feature has been correlated with poor prognosis (Yi et al, 1997;Witton et al, 2003;Tanner et al, 2006). On activation by heregulins, ErbB-3 dimerizes with ErbB-2 and ErbB-1 to generate potent oncogenic receptor heterodimers (Alimandi et al, 1995;Wallasch et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

An ErbB-3 antibody, MP-RM-1, inhibits tumor growth by blocking ligand-dependent and independent activation of ErbB-3/Akt signaling

Sala¹,

Traini²,

D'Egidio³

et al. 2011

Oncogene

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The ErbB receptors, such as ErbB-1 and ErbB-2, have been intensely pursued as targets for cancer therapeutics. Although initially efficacious in a subset of patients, drugs targeting these receptors led invariably to resistance, which is often associated with reactivation of the ErbB-3-PI3K-Akt signaling. This may be overcome by an ErbB-3 ligand that abrogates receptor-mediated signaling. Toward this end, we have generated a mouse monoclonal antibody, MP-RM-1, against the extracellular domain (ECD) of ErbB-3 receptor. Assessment of human tumor cell lines, as well as early passage tumor cells revealed that MP-RM-1 effectively inhibited both NRG-1b-dependent and -independent ErbB-3 activation. The antagonizing effect of MP-RM-1 was of non-competitive type, as binding of [ 125 I]-labeled NRG-1b to ErbB-3 was not influenced by the antibody. MP-RM-1 treatment led, in most instances, to decreased ErbB-3 expression. In addition, MP-RM-1 was able to inhibit the colony formation ability of tumor cells and tumor growth in two human tumor xenograft nude mouse models. Treatment with the antibody was associated with a decreased ErbB-3 and Akt phosphorylation and ErbB-3 expression in the excised tumor tissue. Collectively, these results indicate that MP-RM-1 has the potential to interfere with signaling by ErbB-3 and reinforce the notion that ErbB-3 could be a key target in cancer-drug design.

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ErbB-3 Predicts Survival in Ovarian Cancer

Abstract: HER3 may represent a new prognostic factor in primary epithelial ovarian cancer. Pending validation, exploration of therapeutic strategies to block HER3 could be warranted.

Cited by 191 publications

References 33 publications

The ERBB3 receptor in cancer and cancer gene therapy

The ERBB3 receptor in cancer and cancer gene therapy

Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors

An ErbB-3 antibody, MP-RM-1, inhibits tumor growth by blocking ligand-dependent and independent activation of ErbB-3/Akt signaling

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