Gastrointestinal cancers are responsible for more cancer deaths than any other system of the body. This review summarises how Wnt pathway dysregulation contributes to the development of the most common gastrointestinal cancers, with a particular focus on the nature and frequency of upstream pathway aberrations. Tumors with upstream aberrations maintain a dependency on the presence of functional Wnt ligand, and are predicted to be tractable to inhibitors of Porcupine, an enzyme that plays a key role in Wnt secretion. We summarise available pre-clinical efficacy data from Porcupine inhibitors in vitro and in vivo, as well as potential toxicities and the data from early phase clinical trials. We appraise the rationale for biomarker-defined targeted approaches, as well as outlining future opportunities for combination with other therapeutics.

与身体的任何其他系统相比，胃肠道癌症导致更多的癌症死亡。这篇综述总结了 Wnt 通路失调如何导致最常见的胃肠道癌症的发展，特别关注上游通路异常的性质和频率。具有上游畸变的肿瘤依赖于功能性 Wnt 配体的存在，并且预计会受到 Porcupine 抑制剂的影响，Porcupine 是一种在 Wnt 分泌中起关键作用的酶。我们总结了豪猪抑制剂在体外和体内的可用临床前疗效数据，以及潜在的毒性和早期临床试验的数据。我们评估了生物标志物定义的靶向方法的基本原理，并概述了与其他疗法组合的未来机会。