Nwabo Kamdje Armel Herve, Takam Kamga Paul, Tagne Simo Richard, Vecchio Lorella, Seke Etet Paul Faustin, Muller Jean Marc, Bassi Giulio, Lukong Erique, Kumar Goel Raghuveera, Mbo Amvene Jeremie, Krampera Mauro
Department of Biomedical Sciences, University of Ngaoundere, Ngaoundere 454, Cameroon.
Cancer Biol Med. 2017 May;14(2):109-120. doi: 10.20892/j.issn.2095-3941.2016.0032.
Master developmental pathways, such as Notch, Wnt, and Hedgehog, are signaling systems that control proliferation, cell death, motility, migration, and stemness. These systems are not only commonly activated in many solid tumors, where they drive or contribute to cancer initiation, but also in primary and metastatic tumor development. The reactivation of developmental pathways in cancer stroma favors the development of cancer stem cells and allows their maintenance, indicating these signaling pathways as particularly attractive targets for efficient anticancer therapies, especially in advanced primary tumors and metastatic cancers. Metastasis is the worst feature of cancer development. This feature results from a cascade of events emerging from the hijacking of epithelial-mesenchymal transition, angiogenesis, migration, and invasion by transforming cells and is associated with poor survival, drug resistance, and tumor relapse. In the present review, we summarize and discuss experimental data suggesting pivotal roles for developmental pathways in cancer development and metastasis, considering the therapeutic potential. Emerging targeted antimetastatic therapies based on Notch, Wnt, and Hedgehog pathways are also discussed.
主控发育通路，如Notch、Wnt和Hedgehog，是控制细胞增殖、死亡、运动、迁移和干性的信号系统。这些系统不仅在许多实体瘤中普遍被激活，在实体瘤中它们驱动癌症起始或对其产生影响，而且在原发性和转移性肿瘤发展过程中也被激活。癌症基质中发育通路的重新激活有利于癌症干细胞的发育并使其得以维持，这表明这些信号通路是高效抗癌治疗中特别有吸引力的靶点，尤其是在晚期原发性肿瘤和转移性癌症中。转移是癌症发展最糟糕的特征。这一特征源于转化细胞劫持上皮-间质转化、血管生成、迁移和侵袭所引发的一系列事件，并且与生存率低、耐药性和肿瘤复发相关。在本综述中，我们总结并讨论了实验数据，这些数据表明发育通路在癌症发展和转移中起关键作用，并考虑了其治疗潜力。还讨论了基于Notch、Wnt和Hedgehog通路的新兴靶向抗转移疗法。
