Lineage factors and differentiation states in lung cancer progression

Lung cancer encompasses a heterogeneous group of malignancies. Here we discuss how the remarkable diversity of major lung cancer subtypes is manifested in their transforming cell of origin, oncogenic dependencies, phenotypic plasticity, metastatic competence and response to therapy. More specifically, we review the increasing evidence that links this biological heterogeneity to the deregulation of cell lineage-specific pathways and the transcription factors that ultimately control them. As determinants of pulmonary epithelial differentiation, these poorly characterized transcriptional networks may underlie the etiology and biological progression of distinct lung cancers, while providing insight into innovative therapeutic strategies.

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Acknowledgements

We thank all members of the Nguyen laboratory for their discussions and critical reviews of the manuscript. We apologize for omitting some examples and primary references due to space constraints. Our research is funded by grants from Uniting Against Lung Cancer (to WKCC) and the National Cancer Institute (1R01CA166376, 1R21CA170537 and 1R01CA191489 to DXN).