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Review
. 2020 Aug 1;34(15-16):1017-1032.
doi: 10.1101/gad.338228.120.

Cells of origin of lung cancers: lessons from mouse studies

Giustina Ferone  1 , Myung Chang Lee  2   3 , Julien Sage  2   3 , Anton Berns  1
Affiliations
Review

Cells of origin of lung cancers: lessons from mouse studies

Giustina Ferone et al. Genes Dev. .

Abstract

As one of the most common forms of cancer, lung cancers present as a collection of different histological subtypes. These subtypes are characterized by distinct sets of driver mutations and phenotypic appearance, and they often show varying degrees of heterogenicity, aggressiveness, and response/resistance to therapy. Intriguingly, lung cancers are also capable of showing features of multiple subtypes or converting from one subtype to another. The intertumoral and intratumoral heterogeneity of lung cancers as well as incidences of subtype transdifferentiation raise the question of to what extent the tumor characteristics are dictated by the cell of origin rather than the acquired driver lesions. We provide here an overview of the studies in experimental mouse models that try to address this question. These studies convincingly show that both the cell of origin and the genetic driver lesions play a critical role in shaping the phenotypes of lung tumors. However, they also illustrate that there is far from a direct one-to-one relationship between the cell of origin and the cancer subtype, as most epithelial cells can be reprogrammed toward diverse lung cancer fates when exposed to the appropriate set of driver mutations.

Keywords: LuADC; LuSCC; NSCLC; cell of origin; lung cancer; mouse models.

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Figures

Figure 1.
Figure 1.
Schematic representation showing how mouse lung composition varies from the trachea to the alveolar space. Basal, club, neuroendocrine and AT2 cells are the major differentiated subtypes and have been either engineered or targeted to express tumor driver mutations.
Figure 2.
Figure 2.
Schematic representation of genetic lesions that have resulted in LUAD in mouse models. Targeted cells of origin throughout the lung are also shown.
Figure 3.
Figure 3.
Schematic representation of genetic lesions that have resulted in LSCC in mouse models. Targeted cells of origin throughout the lung are also shown.
Figure 4.
Figure 4.
Schematic representation of genetic lesions that have resulted in SCLC in mouse models. Targeted cells of origin throughout the lung are also shown.
See this image and copyright information in PMC

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References

    1. Adjei AA. 2019. Lung cancer worldwide. J Thorac Oncol 14: 956 10.1016/j.jtho.2019.04.001 - DOI - PubMed
    1. Armstrong SA, Liu SV. 2019. Immune checkpoint inhibitors in small cell lung cancer: a partially realized potential. Adv Ther 36: 1826–1832. 10.1007/s12325-019-01008-2 - DOI - PMC - PubMed
    1. Baggstrom MQ, Qi Y, Koczywas M, Argiris A, Johnson EA, Millward MJ, Murphy SC, Erlichman C, Rudin CM, Govindan R, et al. 2011. A phase II study of AT-101 (Gossypol) in chemotherapy-sensitive recurrent extensive-stage small cell lung cancer. J Thorac Oncol 6: 1757–1760. 10.1097/JTO.0b013e31822e2941 - DOI - PMC - PubMed
    1. Blanpain C. 2013. Tracing the cellular origin of cancer. Nat Cell Biol 15: 126–134. 10.1038/ncb2657 - DOI - PubMed
    1. Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, et al. 2015. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373: 123–135. 10.1056/NEJMoa1504627 - DOI - PMC - PubMed

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