We found that high serum HB-EGF concentrations were significantly associated with poor prognosis in a combined cohort of patients with all stages of ovarian cancer, as well as in a subset of patients with advanced disease.
HER3 is a member of the epidermal growth factor family and was predominantly described as a negative prognostic factor in various solid tumors as well as in ovarian cancer.
Collectively, HB-EGF is a molecular target for the resistance of ovarian cancer to paclitaxel and CRM197 as a HB-EGF-targeted agent might be a chemosensitizing agent for paclitaxel-resistant ovarian carcinoma.
Taken together, our data provide evidence that TNFR1 plays a critical role in ovarian cancer and show that the EGF induced signaling pathway is independent of the TNF-α triggering cascade signal.
Pharmacological inhibition of c-Myc reduced HB-EGF induced glycolytic enzymes implicating a major role of c-Myc in loss of HSulf-1 mediated altered glycolytic pathway in OVCA.
This study reveals the loss of SPRY2 in HGSC and indicates an important tumor-suppressive role for SPRY2 in mediating the stimulatory effect of EGF on human EOC progression.
In agreement with these results, selected genes from the identified signatures were validated in vitro by real time RT-PCR in serous EOC cell lines upon stimulation with EGF.
We conducted a phase II trial to evaluate the activity and tolerability of lapatinib in patients with recurrent or persistent epithelial ovarian cancer (EOC) and to explore the clinical value of expression levels of epidermal growth factor receptors (EGFR), phosphorylated EGFR, HER-2/neu, and Ki-67, and the presence of EGFR mutations.
Epidermal growth factor (EGF) activation of the EGF receptor (EGFR) is an important mediator of cell migration, and aberrant signaling via this system promotes a number of malignancies including ovarian cancer.
Epidermal growth factor (EGF) receptor (EGFR) is frequently elevated in epithelial ovarian cancer, and E-cadherin expression is often reduced in advanced disease.
A similar sALCAM molecule was also found in the ascitic fluids and sera from EOC patients, suggesting that this process also occurs in vivo. sALCAM is constitutively produced by EOC cells, and this process can be enhanced by cell treatment with pervanadate, phorbol 12-myristate 13-acetate (PMA), or epidermal growth factor (EGF), a known growth factor for EOC.
These data suggest that EGF-related peptides function as autocrine growth factors in ovarian carcinoma cells, and that they might represent targets for experimental therapy of ovarian carcinoma.
With the exception of EGF-R and CD31, clonal divergence of the biomarkers evaluated in this study probably does not play a significant role in imparting clinical heterogeneity during the advanced and recurrent stages of epithelial ovarian cancer.