Wnt/β-catenin and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin complex 1 (PI3K/AKT/mTORC1) pathways both are critically involved in colorectal cancer (CRC) development, although they are implicated in the modulation of distinct oncogenic mechanisms. In homeostatic and pathologic conditions, these pathways show a fine regulation based mainly on feedback mechanisms, and are connected at multiple levels involving both upstream and downstream common effectors. The ability of the Wnt/β-catenin and PI3K/AKT/mTORC1 pathways to reciprocally control themselves represents one of the main resistance mechanisms to selective inhibitors in CRC, leading to the hypothesis that in specific settings, particularly in cancer driven by genetic alterations in Wnt/β-catenin signaling, the relationship between Wnt/β-catenin and PI3K/AKT/mTORC1 pathways could be so close that they should be considered as a unique therapeutic target. This review provides an update on the Wnt/β-catenin and PI3K/AKT/mTORC1 pathway interconnections in CRC, describing the main molecular players and the potential implications of combined inhibitors as an approach for CRC chemoprevention and treatment.

Wnt/β-catenin 和磷脂酰肌醇-3-激酶/蛋白激酶 B/雷帕霉素复合物 1 (PI3K/AKT/mTORC1) 通路的哺乳动物靶点都与结直肠癌 (CRC) 的发展密切相关，尽管它们参与调节独特的致癌机制。在稳态和病理条件下，这些通路显示出主要基于反馈机制的精细调节，并在涉及上游和下游共同效应器的多个层次上连接。Wnt/β-catenin 和 PI3K/AKT/mTORC1 通路相互控制自身的能力代表了 CRC 中对选择性抑制剂的主要耐药机制之一，导致假设在特定情况下，特别是在由基因改变驱动的癌症中Wnt/β-连环蛋白信号传导，Wnt/β-catenin 和 PI3K/AKT/mTORC1 通路之间的关系可能如此密切，以至于它们应该被视为一个独特的治疗靶点。本综述提供了关于 CRC 中 Wnt/β-catenin 和 PI3K/AKT/mTORC1 通路互连的更新，描述了主要分子参与者和联合抑制剂作为 CRC 化学预防和治疗方法的潜在影响。