Department of Hematology and Oncology, Cedars Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA.
Target Oncol. 2017 Oct;12(5):623-641. doi: 10.1007/s11523-017-0507-4.
Wnt signaling is an evolutionarily conserved pathway that controls cell-to-cell interactions during embryogenesis. In adults, Wnt signaling plays a role in tissue homeostasis in almost every organ system. Aberrations within this pathway are implicated in a spectrum of human diseases. A variety of perturbations have been described in both solid and hematologic malignancies, lending way to Wnt signaling as a target for anti-cancer therapy. Of particular interest is the role of Wnt signaling in the development and maintenance of cancer stem cells, a rare population of cells that are able to maintain a tumor via self-renewal and thought to be more resistant to chemotherapy than bulk tumor cells. The ability to eradicate cancer stem cells may decrease the risk of cancer relapse and metastasis. A number of therapeutic agents specifically targeting the Wnt pathway have entered clinical trials, either as monotherapy or in combination with chemotherapy. We will provide an overview of agents that have been developed to target the Wnt pathways and a summary of pre-clinical and clinical trials.
Wnt 信号通路是一条进化上保守的通路,它在胚胎发生过程中控制细胞间的相互作用。在成年人中,Wnt 信号通路在几乎所有的器官系统中都发挥着组织内稳态的作用。该通路中的异常与一系列人类疾病有关。在实体瘤和血液恶性肿瘤中已经描述了多种干扰,这使得 Wnt 信号通路成为癌症治疗的一个靶点。特别值得关注的是 Wnt 信号通路在癌症干细胞的发育和维持中的作用,癌症干细胞是一种罕见的细胞群体,能够通过自我更新来维持肿瘤,并且被认为比肿瘤细胞更能抵抗化疗。消除癌症干细胞的能力可能会降低癌症复发和转移的风险。许多专门针对 Wnt 通路的治疗药物已经进入临床试验,无论是单独使用还是与化疗联合使用。我们将概述为靶向 Wnt 通路而开发的药物,并总结临床前和临床试验的结果。