Department of Radiation Oncology, Division of Radiation Biology, 1530 3rd Avenue South, WTI 674 Birmingham, AL 35294-6832, USA.
Immunotherapy. 2009 Mar;1(2):223-9. doi: 10.2217/1750743X.1.2.223.
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.
人胰腺导管腺癌是一种恶性疾病,其发病率和死亡率几乎相等。为了提高患者的生存率,仍然迫切需要有效的诊断和治疗策略。随着结构和功能基因组学的发展,最近的工作集中在使用单克隆抗体的靶向分子治疗上。本综述总结了与胰腺导管腺癌发生、肿瘤生长或化疗耐药相关的肿瘤细胞表面和正常组织基质上的靶分子,以及与调节炎症和宿主免疫反应相关的分子。靶向分子包括细胞表面受体,如表皮生长因子受体、HER2、死亡受体 5 和 IGF-1 受体。还讨论了针对这些靶分子的单克隆抗体单独或与化疗、小分子信号转导抑制剂或放射治疗联合使用的效果,以及毒素或放射性同位素缀合物的使用,以及这些靶向药物在胰腺癌临床试验中的应用信息。尽管单克隆抗体的靶向分子治疗在胰腺癌治疗方面取得了一些进展,特别是在临床前研究中,但要将其应用于提高胰腺癌患者的生存率,还需要进一步研究。