Studies of epidermal growth factor receptor inhibition in breast cancer.

Bundred, Nigel; Chan, Kai Chio; Anderson, Neil G.

doi:10.1677/erc.0.0080183

Cited by 27 publications

(12 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ZD1839 (Iressa, gefitinib) has proven to be useful preclinically and clinically for treating EGFR-expressing tumors, such as non-small cell lung cancer, head and neck cancer, breast cancer, prostate cancer, and others; the general doses used clinically are 250 to 500 mg/d (27)(28)(29)(30). Other EGFR inhibitors, such as Herceptin (trastuzumab), an anti-HER2 monoclonal antibody, have shown activity in a subset of breast cancers (31).…”

Section: Discussionmentioning

confidence: 99%

Proliferation of Human Neuroblastomas Mediated by the Epidermal Growth Factor Receptor

Minturn²,

Hishiki³

et al. 2005

Cancer Research

132

129

View full text Add to dashboard Cite

Neuroblastoma is a common solid tumor of childhood that is derived from the neural crest. Expression of epidermal growth factor (EGF) receptors (EGFRs) has been associated with enhanced cell growth and aggressive behavior in other tumors. Here, we examined the expression profile of EGFRs in neuroblastoma cell lines and primary tumors. We found that all 13 neuroblastoma cell lines examined expressed EGFR1 (HER1), most at readily detectable levels. Low levels of other human EGFR family receptors were also detected in almost all cell lines. All primary tumors examined expressed readily detectable levels of HER1 and HER3 and lower levels of HER2 and HER4. EGF had a significant effect on the proliferation of neuroblastoma cell lines in vitro. EGF treatment (100 ng/mL) of the cell lines SY5Y and NLF significantly increased cell number (P < 0.01). EGF stimulated more cells to enter S and G 2 -M phase, as suggested by flow cytometry, indicating that EGF increases cell number by increasing proliferation, with no appreciable change in apoptosis. EGF exposure resulted in receptor autophosphorylation and activation of both the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT pathways. Exposure to 0.5 Mmol/L ZD1839, a HER1-specific inhibitor, caused a 40% to 50% reduction in the number of SY5Y and NLF cells grown in medium containing 10% fetal bovine serum (P < 0.01). Even at 0.01 Mmol/L, ZD1839 inhibited autophosphorylation of HER1 by EGF. At 0.1 Mmol/L, it also blocked phosphorylation of AKT, but not MAPK, in NLF cells. Additional studies showed that the PI3K/AKT-specific inhibitor LY294002 had a more profound effect than the MAPK-specific inhibitor U0126 in blocking EGF-induced cell proliferation. This suggests that the PI3K/AKT pathway is the main signaling pathway responsible for the proliferation effects of EGF in neuroblastomas. Our results also indicate that ZD1839 is a potent inhibitor of neuroblastoma cell proliferation; therefore, it may be a useful, biologically based therapeutic agent for these tumors. (Cancer Res 2005; 65(21): 9868-75)

show abstract

Section: Discussionmentioning

confidence: 99%

Proliferation of Human Neuroblastomas Mediated by the Epidermal Growth Factor Receptor

Minturn²,

Hishiki³

et al. 2005

Cancer Research

132

129

View full text Add to dashboard Cite

show abstract

“…In addition, ER-negative ductal carcinoma in situ express EGFR and HER-2 (Bundred et al, 2001) which are suggested to be the main receptor pathway associated with epithelial proliferation and survival in the human breast.…”

Section: Discussionmentioning

confidence: 99%

Resistance to chemotherapy via Stat3-dependent overexpression of Bcl-2 in metastatic breast cancer cells

et al. 2002

View full text Add to dashboard Cite

Disruption of apoptosis may allow metastatic cell survival and confer resistance to chemotherapeutic drugs. We have analysed the molecular pathways that activate these survival genes in specific sites of metastasis. Estrogen receptor-negative breast cancer cell line MDA-MB435 and two metastatic sublines derived from lung (435L) and brain (435B) were analysed for the expression of members of the Bcl-2 family of apoptosis regulators. The levels of Bcl-2 were higher in the metastatic sublines than in parental cells, which correlated with the activation of Stat3, but not with the expression and/or activation of known bcl-2 transcription factors (CREB and WT1). In the brain subline, both expression of Bcl-2 and Stat3 activation were induced by epidermal growth factor and abrogated after treatment with kinase inhibitors specific for epidermal growth factor receptor or Jak2. Furthermore, transfection of 435B with a dominant-negative Stat3 markedly reduced the expression of Bcl-2 protein, whereas transient expression of a constitutively active Stat3 increased Bcl-2 in parental 435 cells. In addition, blockade of Stat3 activation by treatment with epidermal growth factor receptor and Jak2 kinase inhibitors or transfection with a dominant negative Stat3, sensitizes 435B cells to chemotherapy-induced apoptosis. Our data suggest that an increased activation of the Stat3 -Bcl-2 pathway in estrogen receptor-negative metastatic breast cancer cell lines confer a survival advantage to these cells and contribute to their chemoresistance.

show abstract

“…These mutual interactions between ER and HER pathways seem to hot-wire the events inducing endocrine resistance in ER-positive breast tumors [17, 18]. For all these reasons, HER-1/EGFR is thought to represent not only a possible prognostic marker but primarily a rational molecular target for a new class of anticancer agents [19,20,21,22]. …”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Prognostic and Predictive Value of HER-1/EGFR in Breast Cancer Patients Participating in a Randomized Study with Dose-Dense Sequential Adjuvant Chemotherapy

Tzaida

Gogas²,

Dafni³

et al. 2007

Oncology

View full text Add to dashboard Cite

Background: To assess the prognostic and predictive significance of HER-1/EGFR protein levels in high-risk patients with breast cancer treated with dose-dense sequential adjuvant chemotherapy. Methods: 595 high-risk breast cancer patients were treated with adjuvant anthracycline-based dose-dense sequential chemotherapy (E-CMF vs. E-T-CMF). Disease-free survival (DFS) was the primary end point. HER-1/EGFR was assessed by immunohistochemistry (IHC) in 312 patients. Results: HER-1/EGFR expression was detected in 54 of 312 patients (17%). Positive expression of HER-1/EGFR was significantly associated with negative receptor status (52 vs. 17%, p < 0.001), worse histological grade (70 vs. 45%, p = 0.001), HER-2 overexpression (46 vs. 27%, p = 0.01) and positive p53 expression (48 vs. 19%, p < 0.001). With a median follow-up of 7 years, the total number of relapses was 105 (34%), and the total number of deaths 69 (22%). The analysis for DFS provides significant evidence that the HER-1/EGFR effect on the risk of disease progression was different according to treatment (interaction p = 0.02). Regarding overall survival, a trend towards a significant difference for an interaction of HER-1/EGFR and treatment was found (p = 0.07). Conclusion: The present study demonstrated a differential effect of positive HER-1/EGFR expression in the two treatment groups, with HER-1/EGFR being a negative prognostic marker in the absence of paclitaxel.

show abstract

Studies of epidermal growth factor receptor inhibition in breast cancer.

Cited by 27 publications

References 26 publications

Proliferation of Human Neuroblastomas Mediated by the Epidermal Growth Factor Receptor

Proliferation of Human Neuroblastomas Mediated by the Epidermal Growth Factor Receptor

Resistance to chemotherapy via Stat3-dependent overexpression of Bcl-2 in metastatic breast cancer cells

Evaluation of the Prognostic and Predictive Value of HER-1/EGFR in Breast Cancer Patients Participating in a Randomized Study with Dose-Dense Sequential Adjuvant Chemotherapy

Contact Info

Product

Resources

About