title: Developmental signalling pathways in lung cancer.
abstract: 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.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21231, USA.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Daniel
authors.forename: Craig D
authors.initials: CD
authors.lastname: Peacock
authors.forename: D Neil
authors.initials: DN
authors.lastname: Watkins
mesh_terms: D000818:Animals; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism; D051154:Wnt2 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D012334:RNA, Neoplasm; D051880:Receptors, Notch; D051155:Wnt1 Protein; D051154:Wnt2 Protein