Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors.
Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors.
复制标题
靶向癌症中的Wnt/β-连环蛋白通路：效应子和抑制剂的更新。
DOI：
10.1016/j.ctrv.2017.11.002
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发表时间：
2018-01
影响因子：
11.8
通讯作者：
Kurzrock R
中科院分区：
文献类型：
--
作者：
Krishnamurthy N;Kurzrock R
Wnt/ β -连环蛋白通路是一个涉及许多重要细胞功能的蛋白家族，如干细胞再生和器官发生。几种细胞内信号转导途径是由Wnt诱导的，特别是Wnt/ β -连环蛋白依赖途径或规范途径和非规范或β -连环蛋白独立途径，后者包括Wnt/Ca2+和平面细胞极性途径（PCP）。Wnt激活发生在肠隐窝底，对干细胞的最佳维持至关重要。结直肠癌显示Wnt信号通路激活的证据，这与肿瘤调节因子APC的功能丧失有关。Wnt激活已在乳腺、肺和造血恶性肿瘤中观察到，并有助于肿瘤复发。Wnt通路与Notch和Sonic Hedgehog通路交叉对话，这对癌症的治疗干预具有重要意义。针对Wnt通路存在重大挑战，包括寻找在细胞修复和组织稳态中不破坏正常体细胞干细胞功能系统的有效药物。在这里，我们全面回顾了Wnt通路及其与Notch和Sonic Hedgehog通路的相互作用。我们介绍了Wnt信号的效应器和抑制剂领域的现状，包括Wnt、Notch和Sonic Hedgehog抑制剂在各种癌症中的临床试验的最新进展。
The Wnt/beta-catenin pathway is a family of proteins that is implicated in many vital cellular functions like stem cell regeneration and organogenesis. Several intra-cellular signal transduction pathways are induced by Wnt, notably the Wnt/beta-catenin dependent pathway or canonical pathway and the non-canonical or beta-catenin-independent pathway, the latter includes the Wnt/Ca2+ and Planar Cell Polarity pathway (PCP). Wnt activation occurs at the intestinal crypt floor, and is critical to optimal maintenance of stem cells. Colorectal cancers show evidence of Wnt signaling pathway activation and this is associated with loss of function of the tumor regulator APC. Wnt activation has been observed in breast, lung, and hematopoietic malignancies and contributes to tumor recurrence. The Wnt pathway cross talks with the Notch and Sonic Hedgehog pathways, which has implications for therapeutic interventions in cancers. There are significant challenges in targeting the Wnt pathway, including finding agents that are efficacious without damaging the system of normal somatic stem cell function in cellular repair and tissue homeostasis. Here, we comprehensively review the Wnt pathway and its interactions with the Notch and Sonic Hedgehog pathways. We present the state of the field in effectors and inhibitors of Wnt signaling, including updates on clinical trials in various cancers with inhibitors of Wnt, Notch, and Sonic Hedgehog.
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影响因子：
4.8
作者：
He, B;You, L;Jablons, DM
通讯作者：
Jablons, DM
DOI：
10.1016/j.ejca.2015.10.070
发表时间：
2016-03
期刊：
European journal of cancer (Oxford, England : 1990)
影响因子：
--
作者：
Giefing M;Wierzbicka M;Szyfter K;Brenner JC;Braakhuis BJ;Brakenhoff RH;Bradford CR;Sorensen JA;Rinaldo A;Rodrigo JP;Takes RP;Ferlito A
通讯作者：
Ferlito A
影响因子：
9.2
作者：
Hart, MJ;de los Santos, R;Polakis, P
通讯作者：
Polakis, P
影响因子：
56.9
作者：
Bilic, Josipa;Huang, Ya-Lin;Niehrs, Christof
通讯作者：
Niehrs, Christof
影响因子：
3.4
作者：
De Jesus-Acosta, Ana;Laheru, Daniel;Maitra, Anirban;Arcaroli, John;Rudek, Michelle A.;Dasari, Arvind;Blatchford, Patrick J.;Quackenbush, Kevin;Messersmith, Wells
通讯作者：
Messersmith, Wells