Breast Cancer Biology Lab, School of Cancer and Pharmaceutical Sciences, King's College London, London, U.K.
Biochem Soc Trans. 2018 Jun 19;46(3):659-668. doi: 10.1042/BST20170400. Epub 2018 May 21.
Currently, there is renewed interest in attempting to recruit the host immune system to eliminate cancers, and within this renewed activity, MUC1 continues to arouse interest. MUC1 has been considered a possible therapeutic target for the past 30 years as it is up-regulated, aberrantly glycosylated and its polarization is lost in many adenocarcinomas. Moreover, MUC1 is expressed by some haematopoietic cancers, including acute myeloid leukaemia and myeloma. Although multiple clinical trials have been initiated and immune responses have been documented, effective clinical benefit worthy of approval for general application has not as yet been achieved. However, this does not appear to have quelled the interest in MUC1 as a therapeutic target, as shown by the increase in the number of MUC1-based clinical trials initiated in 2017 ( Figure 1). As with all translational studies, incorporating new relevant research findings into therapeutic strategy is difficult. Decisions are made to commit to a specific strategy based on the information and data available when the trial is initiated. However, the time required for preclinical studies and early trials can render the founding concept not always appropriate for proceeding to a larger definitive trial. Here, we summarize the attempts made, to date, to bring MUC1 into the world of cancer immunotherapy and discuss how research findings regarding MUC1 structure and function together with expanded knowledge of its interactions with the tumour environment and immune effector cells could lead to improved therapeutic approaches. ppbiost;46/3/659/BST20170400CF1F1BST-2017-0400CF1Figure 1.Number of MUC1-targeted trials initiated each year.
目前,人们重新产生了利用宿主免疫系统来消灭癌症的兴趣,在这种新的活动中,MUC1 继续引起人们的兴趣。在过去的 30 年中,由于 MUC1 上调、异常糖基化,其极性在许多腺癌中丢失,因此被认为是一种潜在的治疗靶点。此外,MUC1 还在一些血液系统癌症中表达,包括急性髓系白血病和骨髓瘤。尽管已经启动了多项临床试验并记录了免疫反应,但尚未获得值得广泛应用的有效临床益处。然而,这似乎并没有抑制人们对 MUC1 作为治疗靶点的兴趣,如图 1 所示,2017 年启动的基于 MUC1 的临床试验数量有所增加。与所有转化研究一样,将新的相关研究结果纳入治疗策略是很困难的。在启动试验时,根据可用的信息和数据做出承诺采用特定策略的决定。然而,临床前研究和早期试验所需的时间可能会导致最初的概念并不总是适合进行更大规模的确定性试验。在这里,我们总结了迄今为止将 MUC1 引入癌症免疫治疗领域的尝试,并讨论了 MUC1 结构和功能的研究结果以及其与肿瘤环境和免疫效应细胞相互作用的扩展知识如何导致改进的治疗方法。ppbiost;46/3/659/BST20170400CF1F1BST-2017-0400CF1图 1.每年启动的 MUC1 靶向试验数量。