Targeting Wnt Signaling for Gastrointestinal Cancer Therapy: Present and Evolving Views.
Targeting Wnt Signaling for Gastrointestinal Cancer Therapy: Present and Evolving Views.
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胃肠道肿瘤治疗的靶向Wnt信号：目前和发展中的观点。
DOI：
10.3390/cancers12123638
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发表时间：
2020-12-04
期刊：
影响因子：
5.2
通讯作者：
Park JI
中科院分区：
文献类型：
--
作者：
Kim MJ;Huang Y;Park JI
Wnt的治疗靶向长期以来一直被建议用于胃肠道（GI）癌症治疗，因为Wnt信号传导的失调与GI癌症相关。然而，由于Wnt信号在人体中的多效性作用，Wnt的治疗靶向仍然具有挑战性。因此，Wnt信号传导的靶向策略不断发展。目前靶向Wnt信号传导用于癌症治疗的流程集中在增加药物的特异性和与其他癌症药物的组合治疗，以最大限度地减少副作用并提高疗效。此外，关于β-连环蛋白悖论的知识的增加已经扩大了可以用Wnt靶向疗法治疗的病例，而不是严格考虑Wnt上游和下游突变。在这里，我们讨论了这些不断发展的观点，靶向Wnt信号转导和描述的例子，目前的临床试验。Wnt信号调控组织发育、稳态和再生。然而，Wnt的异常激活促进肿瘤发生。尽管正在努力操纵Wnt信号传导，但Wnt信号传导的治疗靶向仍然具有挑战性。在这篇综述中，我们提供了一个概述目前的临床试验，以目标Wnt信号，主要集中在胃肠道肿瘤。此外，我们还讨论了针对Wnt信号传导进行癌症治疗的注意事项和替代策略。
Therapeutic targeting of Wnt has long been suggested for gastrointestinal (GI) cancer treatment because deregulation of Wnt signaling is associated with GI cancers. However, therapeutic targeting of Wnt is still challenging because of the pleiotropic roles of Wnt signaling in the human body. Thus, targeting strategies of Wnt signaling are continuously evolving. The current flows of targeting Wnt signaling for cancer treatment are focused on increasing the specificity of drugs and combinatory treatment with other cancer drugs that minimize side effects and increase efficacy. Additionally, increased knowledge about the β-catenin paradox has expanded the cases that can be treated with Wnt targeting therapy, not strictly considering Wnt upstream and downstream mutations. Here, we discuss these evolving views of targeting Wnt signaling and describe examples of current clinical trials. Wnt signaling governs tissue development, homeostasis, and regeneration. However, aberrant activation of Wnt promotes tumorigenesis. Despite the ongoing efforts to manipulate Wnt signaling, therapeutic targeting of Wnt signaling remains challenging. In this review, we provide an overview of current clinical trials to target Wnt signaling, with a major focus on gastrointestinal cancers. In addition, we discuss the caveats and alternative strategies for therapeutically targeting Wnt signaling for cancer treatment.
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