Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha.
Studies show that overexpressed epidermal growth factor receptor (EGFR) is a common occurrence, linking this to the progression of pancreatic cancer, although the association between its expression and the survival rate is rather controversial.
Although aberrant epidermal growth factor receptor (EGFR), Src, and signal transducer and activator of transcription 3 (Stat3) are implicated in pancreatic cancer, therapies that target only one of these entities are undermined by signaling cross-talk.
Erlotinib is used to inhibit the epidermal growth factor receptor for the treatment of pancreatic cancer; however, erlotinib resistance is a major issue and the mechanisms underlying the development of erlotinib resistance remain unclear.
Tyrosine kinase inhibitors (TKIs) that target epidermal growth factor receptor (EGFR) have dramatically improved progression-free survival in non-small-cell lung cancer (NSCLC) patients who carry sensitizing EGFR-activating mutations and in patients with breast and pancreatic cancers.
However, gemcitabine, paclitaxel, or cisplatin treatment enhanced the Akt activation, heterodimer formation of EGFR with HER3, and secretion of amphiregulin, indicating that the presence of gemcitabine promoted the activity of targeted molecules including amphiregulin, Akt, and HER3 for pancreatic cancer therapy.
The purpose of this study was to determine whether inhibition of the epidermal growth factor receptor (EGFR) is a plausible therapeutic strategy in pancreatic cancer.
Given the emerging role of statins in overcoming resistance to anti-EGFR treatment, further studies are justified to evaluate the efficacy and safety of combined simvastatin and anti-EGFR agents, such as erlotinib or cetuximab, plus gemcitabine for treating advanced pancreatic cancer.
Preclinical and clinical studies have revealed that ErbB family for example epidermal growth factor receptor (EGFR) is a validated molecular target for pancreatic cancer prevention and therapy.
Taken together, the results indicate that rhein offers a novel blueprint for pancreatic cancer therapy, particularly when combined with EGFR inhibitors.
In addition, knock-down of EGFR by EGFR siRNA transfection of parental AsPC-1 cells and AsPC-1 cells stably transfected with pre-miR-146a resulted in decreased invasive capacity, which was further confirmed by reduced luciferase activity in cells transfected with pMIR-Luc reporter vector containing miR-146a binding site.