Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5870, U.S.A.
Curr Pharm Des. 2012;18(17):2472-81. doi: 10.2174/13816128112092472.
The prognosis of pancreatic cancer (PC) patients is very poor with a five-year survival of less than 5%. One of the major challenges in developing new therapies for PC is the lack of expression of specific markers by pancreatic tumor cells. Mucins are heavily Oglycosylated proteins characterized by the presence of short stretches of amino acid sequences repeated several times in tandem. The expression of several mucins including MUC1, MUC4, MUC5AC, and MUC16 is strongly upregulated in PC. Recent studies have also demonstrated a link between the aberrant expression and differential overexpression of mucin glycoproteins to the initiation, progression, and poor prognosis of the disease. These studies have led to increasing recognition of mucins as potential diagnostic markers and therapeutic targets in PC. In this focused review we present an overview of the therapies targeting mucins in PC, including immunotherapy (i.e. vaccines, antibodies, and radioimmunoconjugates), gene therapy, and other novel therapeutic strategies.
胰腺癌(PC)患者的预后非常差,五年生存率不足 5%。开发 PC 新疗法的主要挑战之一是胰腺肿瘤细胞缺乏特异性标志物的表达。粘蛋白是一种高度糖基化的蛋白质,其特征是存在短的氨基酸序列重复多次串联。几种粘蛋白的表达包括 MUC1、MUC4、MUC5AC 和 MUC16 在 PC 中强烈上调。最近的研究还表明,粘蛋白糖蛋白的异常表达和差异过表达与疾病的发生、进展和预后不良之间存在关联。这些研究使得粘蛋白成为 PC 潜在的诊断标志物和治疗靶点。在本专题综述中,我们概述了针对 PC 中粘蛋白的治疗方法,包括免疫疗法(即疫苗、抗体和放射性免疫偶联物)、基因疗法和其他新型治疗策略。