Daniel Vincent C, Peacock Craig D, Watkins D Neil
Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21231, USA.
Respirology. 2006 May;11(3):234-40. doi: 10.1111/j.1440-1843.2006.00838.x.
Hedgehog, Notch and Wnt signalling are all essential for axial patterning and progenitor cell fates in signalling pathways conserved from flies to humans. Aberrant activation of these pathways is observed in a wide variety of cancers, suggesting that these embryonic signalling pathways contribute in a fundamental way to the evolution and maintenance of a malignant phenotype. Because all three of these pathways participate in lung development, recent studies have begun to explore the connection between lung development, airway epithelial repair and lung cancer. Development, repair and malignant transformation of the neuroendocrine lineage are all accompanied by aberrant Hedgehog pathway activation, whereas Notch and Wnt signalling may be important in other airway cell types. Small molecule targeting of these pathways may provide therapeutic opportunities in lung cancer. The plant-derived alkaloid cyclopamine is a naturally occurring Hedgehog pathway inhibitor that shows therapeutic promise in small cell lung cancer, a highly aggressive neuroendocrine tumour. A more detailed understanding of how embryonic signalling pathways participate in airway epithelial repair and tumourigenesis may reveal more novel therapeutic vulnerabilities in lung cancer.
刺猬信号通路、Notch信号通路和Wnt信号通路对于从果蝇到人类保守的信号通路中的轴向模式形成和祖细胞命运都至关重要。在多种癌症中都观察到这些通路的异常激活，这表明这些胚胎信号通路在恶性表型的演变和维持中起着根本作用。由于这三种通路都参与肺发育，最近的研究开始探索肺发育、气道上皮修复与肺癌之间的联系。神经内分泌谱系的发育、修复和恶性转化都伴随着刺猬信号通路的异常激活，而Notch和Wnt信号通路可能在其他气道细胞类型中起重要作用。对这些通路进行小分子靶向可能为肺癌提供治疗机会。植物来源的生物碱环杷明是一种天然存在的刺猬信号通路抑制剂，在小细胞肺癌（一种高度侵袭性的神经内分泌肿瘤）中显示出治疗前景。更详细地了解胚胎信号通路如何参与气道上皮修复和肿瘤发生，可能会揭示肺癌中更多新的治疗弱点。
