Monoclonal Antibodies in the Treatment of Pancreatic Cancer

Abstract

Human pancreatic cancer is a malignant disease with almost equal incidence and mortality. Effective diagnostic and therapeutic strategies are still urgently needed to improve its survival rate. With advances in structural and functional genomics, recent work has focused on targeted molecular therapy using monoclonal antibodies. This review summarizes the target molecules on the tumor cell surface and normal tissue stroma, which are related to pancreatic cancer oncogenesis, tumor growth or resistance to chemotherapy, as well as molecules involved in regulating inflammation and host immunoresponses. Targeted molecules include cell-surface receptors, such as the EGF receptor, HER2, death receptor 5 and IGF-1 receptor. Effects of monoclonal antibodies against these target molecules alone or in combination with chemotherapy, small-molecule signal transduction inhibitors, or radiation therapy are also discussed. Also discussed are the use of toxin or radioisotope conjugates, and information relating to the use of these targeting agents in pancreatic cancer clinical trials. Although targeted molecular therapy with monoclonal antibodies has made some progress in pancreatic cancer treatment, especially in preclinical studies, its clinical application to improve the survival rate of pancreatic cancer patients requires further investigation. Keywordscancer therapy; immunotherapy; monoclonal antibody; pancreatic cancer Pancreatic cancer remains a disease with high mortality despite numerous efforts that have been made to improve its survival rates. In a recent analysis using a database from 1973 to 2003 based on modeled period analysis, 5-year survival of pancreatic cancer patients was 7.1% and 10-year survival was below 5% [1]. The survival rate is apparently related to the disease stage with a low rate at 1.6-3.3% among patients with distant metastases [1,2]. Early diagnosis and effective treatment to control the advanced stages of disease may prolong the survival rate of pancreatic cancer [3]. The search for effective treatment of pancreatic cancer has involved in-depth translational research for decades. With the achievements made in molecular biology and cell biology, studies have focused on structural genomics, which have evolved to functional genomics (proteomics) in recent years [4]. Extensive studies to explore molecular mechanisms involved in pancreatic cancer oncogenesis, cancer stem cells, cell proliferation control and metastasis supplied valuable information and directed the treatment strategies towards targeted therapies. In targeted therapies, tumor-associated or tumor-specific proteins were targeted and their roles in corresponding signal transduction pathways were investigated [5]. Targeted therapies could be accomplished by using specific monoclonal antibodies (mAbs) against these proteins or by pathway-specific small-molecule inhibitors [5]. In this review, we focus on the application of mAbs in human pancreatic cancer treatment.Ideally, the cellular targets in the targeted therapies should be ex...

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