Title:EGFR as a Potential Target for the Treatment of Pancreatic Cancer: Dilemma and Controversies
Volume: 15
Issue: 14
Author(s): Reza Nedaeinia, Amir Avan, Mostafa Manian, Rasoul Salehi and Majid Ghayour-Mobarhan
Affiliation:
关键词:
表皮生长因子受体，表皮生长因子受体靶向治疗，胰腺癌，耐药机制
摘要: Pancreatic Ductal Adenocarcinoma (PDAC) is among the most lethal solid tumors with grim prognosis. This
dismal outcome can partially be explained by the resistance to currently available chemotherapy regimens or the failure of
most anticancer agents, which prompted the development of new and effective therapeutic-approaches, such as inhibitors
of the epidermal growth factor receptor (EGFR). Some of these EGFR inhibitors (e.g., erlotinib) are approved for lungcancer,
however available data are inconclusive for treatment of pancreatic cancer patients with EGFR-targeted-therapies.
Here we describe the critical role of EGFR pathway in pancreatic-cancer, strategies to enhance the effectiveness of EGFRinhibitors
as well as the preclinical/clinical studies with particular emphasis on recent findings with monoclonal antibodies
and tyrosine-inhibitors. Several combinations of EGFR inhibitors with other agents illustrate inhibition of tumor-induced
angiogenesis and cell growth. Moreover, combination of erlotinib with gemcitabine showed statistically significance in
overall-survival, compared to gemcitabine-alone. However high cost, little survival gain and increased risk of toxicities
have limited its efficacy. Considering the multiple genetic mutations and the crosstalk of signaling pathways, (1) development
of multiple targeted-therapies; (2) identification of predictive-biomarkers; and (3) those patients who are most
likely benefit from therapy, could provide valuable direction for the clinical development of EGFR inhibitors. Moreover
further preclinical/clinical studies are warranted to identify determinants of the activity of EGFR-inhibitors and mechanisms
leading to resistance to EGFR inhibitors, through the analysis of genetic and environmental alterations affecting
EGFR and parallel pro-cancer pathways. These studies will be critical to improve the efficacy and selectivity of current
anticancer strategies targeting EGFR in pancreatic cancer.
