Development and Mechanistic Insight into the Enhanced Cytotoxic Potential of Parvifloron D Albumin Nanoparticles in EGFR-Overexpressing Pancreatic Cancer Cells.
Epidermal growth factor receptor (EGFR) is overexpressed in a variety of human malignancies, including pancreatic cancer, breast cancer, colon cancer, and non-small cell lung cancer.
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.
Erlotinib marginally improves survival when administered continuously with gemcitabine to patients with advanced pancreatic cancer; however, preclinical data suggest that there is antagonism between chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors when these are delivered concurrently.
Furthermore, we investigated the impact of overexpression and small molecule inhibition on Sirt1 in pancreatic cancer cell culture models including combinatorial treatment with chemotherapy and EGFR-inhibition.
Gemcitabine is the standard first line of therapy for pancreatic cancer but has limited efficacy due to inherent or rapid development of resistance and combining EGFR inhibitors with this regimen results in only a modest clinical benefit.
Given recent reports of TKI-responsive cases of esophageal and pancreatic cancer, this study was designed to determine the prevalence of EGFR mutations in these gastrointestinal cancers.
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.
Here, we describe an EGFR-mediated signaling pathway that regulates human pancreatic carcinoma cell invasion and metastasis, yet does not influence the growth of primary tumors.
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.
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.
In conclusion, our studies will enhance the translational acquaintance of pan-EGFR inhibitors for combinational therapies to combat against lethal pancreatic cancer.
In contrast, the growth factor receptor genes c-erbB-1 and c-erbB-2 are differentially regulated in both tumor entities adding further evidence that pancreatic cancer is biologically different from the cancer of papilla of Vater.
In this article, we conduct a comprehensive review of the literature on the expression pattern, prognostic significance and predictive value of EGFR family members, IGF-IR and their ligands in pancreatic cancer.