The Wnt/beta-catenin pathway is a family of proteins that is implicated in many vital cellular functions such as 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.

Wnt/β-连环蛋白途径是一个蛋白质家族，涉及许多重要的细胞功能，例如干细胞再生和器官发生。Wnt 诱导多种细胞内信号转导途径，特别是 Wnt/β-连环蛋白依赖性途径或规范途径以及非规范或 β-连环蛋白非依赖性途径；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，对于干细胞的最佳维持至关重要。结直肠癌显示出 Wnt 信号通路激活的证据，这与肿瘤调节剂 APC 功能的丧失有关。在乳腺癌、肺癌和造血系统恶性肿瘤中观察到 Wnt 激活，并导致肿瘤复发。Wnt 通路与 Notch 和 Sonic Hedgehog 通路相互作用，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，包括寻找有效且不损害细胞修复和组织稳态中正常成体干细胞功能系统的药物。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 信号传导效应器和抑制剂领域的现状，包括使用 Wnt、Notch 和 Sonic Hedgehog 抑制剂在各种癌症中进行的临床试验的最新情况。