Serological and immunohistochemical HER-2/neu statuses do not correlate and lack prognostic value for ovarian cancer patients

Hoopmann, Markus; Sachse, Konrad; Valter, Markus M.; Becker, Martina; Neumann, Rainer; Ortmann, Monika; Göhring, Uwe-Jochen; Thomas, Anke; Mallmann, Peter; Schöndorf, Thomas

doi:10.1111/j.1365-2354.2009.01112.x

Cited by 13 publications

(6 citation statements)

References 31 publications

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“…In a multi‐center randomized phase III trial of platinum‐based combinatorial chemotherapy, ErbB2 amplification was only seen in small percentage of participants and was not associated with response (Farley et al, 2009). Additionally, several studies have shown that ErbB2 status is not associated with any clinicopathological parameter such as progression free survival, stable disease, or overall survival in EOC (de Graeff et al, 2008; Hoopmann et al, 2010). These studies suggest that ErbB2's role in EOC may not be as important as our model interpreted it to be.…”

Section: Resultsmentioning

confidence: 99%

A multivariate model of ErbB network composition predicts ovarian cancer cell response to canertinib

Prasasya

Vang

Kreeger

2011

Biotech & Bioengineering

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Identifying the optimal treatment strategy for cancer is an important challenge, particularly for complex diseases like epithelial ovarian cancer (EOC) that are prone to recurrence. In this study we developed a quantitative, multivariate model to predict the extent of ovarian cancer cell death following treatment with an ErbB inhibitor (canertinib, CI-1033). A partial least squares regression model related the levels of ErbB receptors and ligands at the time of treatment to sensitivity to CI-1033. In this way, the model mimics the clinical problem by incorporating only information that would be available at the time of drug treatment. The full model was able to fit the training set data and was predictive. Model analysis demonstrated the importance of including both ligand and receptor levels in this approach, consistent with reports of the role of ErbB autocrine loops in EOC. A reduced multi-protein model was able to predict CI-1033 sensitivity of six distinct EOC cell lines derived from the three subtypes of EOC, suggesting that quantitatively characterizing the ErbB network could be used to broadly predict EOC response to CI-1033. Ultimately, this systems biology approach examining multiple proteins has the potential to uncover multivariate functions to identify subsets of tumors that are most likely to respond to a targeted therapy.

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Section: Resultsmentioning

confidence: 99%

A multivariate model of ErbB network composition predicts ovarian cancer cell response to canertinib

Prasasya

Vang

Kreeger

2011

Biotech & Bioengineering

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“…However, consistent with a mono-epitopic interaction with the antigen, we did not observe in vitro or in vivo degranulation in the presence of ECD HER2 . A serum concentration of ECD HER2 above 15 ng/ml is considered to be elevated in cancer patients, with highly elevated levels being above 100 ng/ml [58, 62]. The average concentration in the serum of patients with advanced disease is 35–40 ng/ ml [58, 59].…”

Section: Discussionmentioning

confidence: 99%

Targeting HER2/neu with a fully human IgE to harness the allergic reaction against cancer cells

Daniels

Leuchter

Quintero

et al. 2011

Cancer Immunol Immunother

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Breast and ovarian cancer are two of the leading causes of cancer deaths among women in the United States. Overexpression of the HER2/neu oncoprotein has been reported in patients affected with breast and ovarian cancers, and is associated with poor prognosis. To develop a novel targeted therapy for HER2/neu expressing tumors, we have constructed a fully human IgE with the variable regions of the scFv C6MH3-B1 specific for HER2/neu. This antibody was expressed in murine myeloma cells and was properly assembled and secreted. The Fc region of this antibody triggers in vitro degranulation of rat basophilic cells expressing human FcεRI (RBL SX-38) in the presence of murine mammary carcinoma cells that express human HER2/neu (D2F2/E2), but not the shed (soluble) antigen (ECDHER2) alone. This IgE is also capable of inducing passive cutaneous anaphylaxis in a human FcεRIα transgenic mouse model, in the presence of a cross-linking antibody, but not in the presence of soluble ECDHER2. Additionally, IgE enhances antigen presentation in human dendritic cells and facilitates cross-priming, suggesting that the antibody is able to stimulate a secondary T-cell antitumor response. Furthermore, we show that this IgE significantly prolongs survival of human FcεRIα transgenic mice bearing D2F2/E2 tumors. We also report that the anti-HER2/neu IgE is well tolerated in a preliminary study conducted in Macaca fascicularis (cynomolgus) monkeys. In summary, our results suggest that this IgE should be further explored as a potential therapeutic against HER2/ neu overexpressing tumors, such as breast and ovarian cancers.

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“…This detection rate is quite reasonable because HER-2/neu overexpression has been shown in primary ovarian tumor tissue in approximately 20% of cases. 33 It often has been asked whether surgery could contribute to the dissemination of tumor cells into the blood circulation. For ovarian cancer, the postoperative residual tumor is the most important prognostic factor.…”

Section: Characterization Of Ctcmentioning

confidence: 99%

Molecular Profiling and Prognostic Relevance of Circulating Tumor Cells in the Blood of Ovarian Cancer Patients at Primary Diagnosis and After Platinum-Based Chemotherapy

Aktas

Kasimir‐Bauer

Heubner

et al. 2011

International Journal of Gynecological Cancer

101

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Serological and immunohistochemical HER-2/neu statuses do not correlate and lack prognostic value for ovarian cancer patients

Cited by 13 publications

References 31 publications

A multivariate model of ErbB network composition predicts ovarian cancer cell response to canertinib

A multivariate model of ErbB network composition predicts ovarian cancer cell response to canertinib

Targeting HER2/neu with a fully human IgE to harness the allergic reaction against cancer cells

Molecular Profiling and Prognostic Relevance of Circulating Tumor Cells in the Blood of Ovarian Cancer Patients at Primary Diagnosis and After Platinum-Based Chemotherapy

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