1932

Abstract

Lung cancer continues to be the number one cancer killer. Despite a surge of therapeutic advances in recent years, lung cancer remains fatal when it presents at a stage too advanced for surgical resection. In part, this is due to the disappointing reality of inevitable drug resistance in the face of highly effective, mutation-specific chemotherapy and the limited efficacy of immune checkpoint blockade. Yet, with the increasing application and integration of diverse genomic profiling approaches and the advent of high-content single-cell technologies, the mechanisms of lung cancer initiation, evolution, spread, and resistance are being unraveled at unprecedented resolution. Increasingly sophisticated mouse genetic, xenotransplantation, and ex vivo assays are also enabling functional validation and empiric screening of new therapeutic candidates. In this review, I highlight recent insights into the genetic, cellular, and molecular mechanisms of lung cancer and relate them to the normal biology of the developing and mature lung.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cancerbio-070820-032858
2021-03-04
2024-06-14
Loading full text...

Full text loading...

/deliver/fulltext/cancerbio/5/1/annurev-cancerbio-070820-032858.html?itemId=/content/journals/10.1146/annurev-cancerbio-070820-032858&mimeType=html&fmt=ahah

Literature Cited

  1. Acha-Sagredo A, Uko B, Pantazi P, Bediaga NG, Moschandrea C et al. 2020. Long non-coding RNA dysregulation is a frequent event in non-small cell lung carcinoma pathogenesis. Br. J. Cancer 122:1050–58
    [Google Scholar]
  2. Akiri G, Cherian MM, Vijayakumar S, Liu G, Bafico A, Aaronson SA 2009. Wnt pathway aberrations including autocrine Wnt activation occur at high frequency in human non-small-cell lung carcinoma. Oncogene 28:2163–72
    [Google Scholar]
  3. Alam H, Tang M, Maitituoheti M, Dhar SS, Kumar M et al. 2020. KMT2D deficiency impairs super-enhancers to confer a glycolytic vulnerability in lung cancer. Cancer Cell 37:599–617.e7
    [Google Scholar]
  4. Arbour KC, Jordan E, Kim HR, Dienstag J, Yu HA et al. 2018. Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer. Clin. Cancer Res. 24:334–40
    [Google Scholar]
  5. Balasooriya GI, Goschorska M, Piddini E, Rawlins EL 2017. FGFR2 is required for airway basal cell self-renewal and terminal differentiation. Development 144:1600–6
    [Google Scholar]
  6. Barriga EH, Franze K, Charras G, Mayor R 2018. Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo. Nature 554:523–27
    [Google Scholar]
  7. Berger MF, Mardis ER. 2018. The emerging clinical relevance of genomics in cancer medicine. Nat. Rev. Clin. Oncol. 15:353–65
    [Google Scholar]
  8. Berry MF, Gao R, Kunder CA, Backhus L, Khuong A et al. 2018. Presence of even a small ground-glass component in lung adenocarcinoma predicts better survival. Clin. Lung Cancer 19:e47–51
    [Google Scholar]
  9. Best SA, Ding S, Kersbergen A, Dong X, Song JY et al. 2019. Distinct initiating events underpin the immune and metabolic heterogeneity of KRAS-mutant lung adenocarcinoma. Nat. Commun. 10:4190
    [Google Scholar]
  10. Bowen ME, McClendon J, Long HK, Sorayya A, Van Nostrand JL et al. 2019. The spatiotemporal pattern and intensity of p53 activation dictates phenotypic diversity in p53-driven developmental syndromes. Dev. Cell 50:212–28.e6
    [Google Scholar]
  11. Cai J, Fang L, Huang Y, Li R, Xu X et al. 2017. Simultaneous overactivation of Wnt/β-catenin and TGFβ signalling by miR-128–3p confers chemoresistance-associated metastasis in NSCLC. Nat. Commun. 8:15870
    [Google Scholar]
  12. Camolotto SA, Pattabiraman S, Mosbruger TL, Jones A, Belova VK et al. 2018. FoxA1 and FoxA2 drive gastric differentiation and suppress squamous identity in NKX2–1-negative lung cancer. eLife 7:e38579
    [Google Scholar]
  13. Chae YK, Chang S, Ko T, Anker J, Agte S et al. 2018. Epithelial-mesenchymal transition (EMT) signature is inversely associated with T-cell infiltration in non-small cell lung cancer (NSCLC). Sci. Rep. 8:2918
    [Google Scholar]
  14. Chen D, Mao Y, Wen J, She Y, Zhu E et al. 2019. Tumor spread through air spaces in non-small cell lung cancer: a systematic review and meta-analysis. Ann. Thorac. Surg. 108:945–54
    [Google Scholar]
  15. Chen H, Carrot-Zhang J, Zhao Y, Hu H, Freeman SS et al. 2019. Genomic and immune profiling of pre-invasive lung adenocarcinoma. Nat. Commun. 10:5472
    [Google Scholar]
  16. Chen HJ, Poran A, Unni AM, Huang SX, Elemento O et al. 2019. Generation of pulmonary neuroendocrine cells and SCLC-like tumors from human embryonic stem cells. J. Exp. Med. 216:674–87
    [Google Scholar]
  17. Chen J, Yang H, Teo ASM, Amer LB, Sherbaf FG et al. 2020. Genomic landscape of lung adenocarcinoma in East Asians. Nat. Genet. 52:177–86
    [Google Scholar]
  18. Chung WJ, Daemen A, Cheng JH, Long JE, Cooper JE et al. 2017. Kras mutant genetically engineered mouse models of human cancers are genomically heterogeneous. PNAS 114:E10947–55
    [Google Scholar]
  19. Cicchini M, Buza EL, Sagal KM, Gudiel AA, Durham AC, Feldser DM 2017. Context-dependent effects of amplified MAPK signaling during lung adenocarcinoma initiation and progression. Cell Rep 18:1958–69
    [Google Scholar]
  20. Corces MR, Granja JM, Shams S, Louie BH, Seoane JA et al. 2018. The chromatin accessibility landscape of primary human cancers. Science 362:eaav1898
    [Google Scholar]
  21. Corcoran RB, Chabner BA. 2018. Application of cell-free DNA analysis to cancer treatment. N. Engl. J. Med. 379:1754–65
    [Google Scholar]
  22. D'Amico S, Shi J, Martin BL, Crawford HC, Petrenko O, Reich NC 2018. STAT3 is a master regulator of epithelial identity and KRAS-driven tumorigenesis. Genes Dev 32:1175–87
    [Google Scholar]
  23. Denny SK, Yang D, Chuang CH, Brady JJ, Lim JS et al. 2016. Nfib promotes metastasis through a widespread increase in chromatin accessibility. Cell 166:328–42
    [Google Scholar]
  24. Desai TJ, Brownfield DG, Krasnow MA 2014. Alveolar progenitor and stem cells in lung development, renewal and cancer. Nature 507:190–94
    [Google Scholar]
  25. Duclos GE, Teixeira VH, Autissier P, Gesthalter YB, Reinders-Luinge MA et al. 2019. Characterizing smoking-induced transcriptional heterogeneity in the human bronchial epithelium at single-cell resolution. Sci. Adv. 5:eaaw3413
    [Google Scholar]
  26. Ferone G, Song JY, Krijgsman O, van der Vliet J, Cozijnsen M et al. 2020. FGFR1 oncogenic activation reveals an alternative cell of origin of SCLC in Rb1/p53 mice. Cell Rep 30:3837–50.e3
    [Google Scholar]
  27. Ferone G, Song JY, Sutherland KD, Bhaskaran R, Monkhorst K et al. 2016. SOX2 is the determining oncogenic switch in promoting lung squamous cell carcinoma from different cells of origin. Cancer Cell 30:519–32
    [Google Scholar]
  28. Galan-Cobo A, Sitthideatphaiboon P, Qu X, Poteete A, Pisegna MA et al. 2019. LKB1 and KEAP1/NRF2 pathways cooperatively promote metabolic reprogramming with enhanced glutamine dependence in KRAS-mutant lung adenocarcinoma. Cancer Res 79:3251–67
    [Google Scholar]
  29. George J, Walter V, Peifer M, Alexandrov LB, Seidel D et al. 2018. Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors. Nat. Commun. 9:1048
    [Google Scholar]
  30. Gerstung M, Jolly C, Leshchiner I, Dentro SC, Gonzalez S et al. 2020. The evolutionary history of 2,658 cancers. Nature 578:122–28
    [Google Scholar]
  31. Gocheva V, Naba A, Bhutkar A, Guardia T, Miller KM et al. 2017. Quantitative proteomics identify Tenascin-C as a promoter of lung cancer progression and contributor to a signature prognostic of patient survival. PNAS 114:E5625–34
    [Google Scholar]
  32. Gong X, Yi J, Carmon KS, Crumbley CA, Xiong W et al. 2015. Aberrant RSPO3-LGR4 signaling in Keap1-deficient lung adenocarcinomas promotes tumor aggressiveness. Oncogene 34:4692–701
    [Google Scholar]
  33. Goto N, Fukuda A, Yamaga Y, Yoshikawa T, Maruno T et al. 2019. Lineage tracing and targeting of IL17RB+ tuft cell-like human colorectal cancer stem cells. PNAS 116:12996–3005
    [Google Scholar]
  34. Guan H, Zhu T, Wu S, Liu S, Liu B et al. 2019. Long noncoding RNA LINC00673-v4 promotes aggressiveness of lung adenocarcinoma via activating WNT/β-catenin signaling. PNAS 116:14019–28
    [Google Scholar]
  35. Guerra C, Mijimolle N, Dhawahir A, Dubus P, Barradas M et al. 2003. Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context. Cancer Cell 4:111–20
    [Google Scholar]
  36. Guo X, Zhang Y, Zheng L, Zheng C, Song J et al. 2018. Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing. Nat. Med. 24:978–85
    [Google Scholar]
  37. Haas M, Gomez Vazquez JL, Sun DI, Tran HT, Brislinger M et al. 2019. ΔN-Tp63 mediates Wnt/β-catenin-induced inhibition of differentiation in basal stem cells of mucociliary epithelia. Cell Rep 28:3338–52.e6
    [Google Scholar]
  38. Hashimoto S, Chen H, Que J, Brockway BL, Drake JA et al. 2012. β-Catenin–SOX2 signaling regulates the fate of developing airway epithelium. J. Cell Sci. 125:932–42
    [Google Scholar]
  39. Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA et al. 2018a. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N. Engl. J. Med. 378:2093–104
    [Google Scholar]
  40. Hellmann MD, Nathanson T, Rizvi H, Creelan BC, Sanchez-Vega F et al. 2018b. Genomic features of response to combination immunotherapy in patients with advanced non-small-cell lung cancer. Cancer Cell 33:843–52.e4
    [Google Scholar]
  41. Hoadley KA, Yau C, Hinoue T, Wolf DM, Lazar AJ et al. 2018. Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer. Cell 173:291–304.e6
    [Google Scholar]
  42. Hou Z, Wu Q, Sun X, Chen H, Li Y et al. 2019. Wnt/Fgf crosstalk is required for the specification of basal cells in the mouse trachea. Development 146:dev171496
    [Google Scholar]
  43. Huang YH, Klingbeil O, He XY, Wu XS, Arun G et al. 2018. POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer. Genes Dev 32:915–28
    [Google Scholar]
  44. Jackute J, Zemaitis M, Pranys D, Sitkauskiene B, Miliauskas S et al. 2018. Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to prognosis of non-small cell lung cancer. BMC Immunol 19:3
    [Google Scholar]
  45. Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK et al. 2017. Tracking the evolution of non-small-cell lung cancer. N. Engl. J. Med. 376:2109–21
    [Google Scholar]
  46. Jin C, Lagoudas GK, Zhao C, Bullman S, Bhutkar A et al. 2019. Commensal microbiota promote lung cancer development via γδ T cells. Cell 176:998–1013.e16
    [Google Scholar]
  47. Johnson L, Mercer K, Greenbaum D, Bronson RT, Crowley D et al. 2001. Somatic activation of the K-ras oncogene causes early onset lung cancer in mice. Nature 410:1111–16
    [Google Scholar]
  48. Jones PA, Issa JP, Baylin S 2016. Targeting the cancer epigenome for therapy. Nat. Rev. Genet. 17:630–41
    [Google Scholar]
  49. Juan J, Muraguchi T, Iezza G, Sears RC, McMahon M 2014. Diminished WNT → β-catenin → c-MYC signaling is a barrier for malignant progression of BRAFV600E-induced lung tumors. Genes Dev 28:561–75
    [Google Scholar]
  50. Juul NH, Stockman CA, Desai TJ 2020. Niche cells and signals that regulate lung alveolar stem cells in vivo. Cold Spring Harb. Perspect. Biol.
    [Google Scholar]
  51. Kadara H, Sivakumar S, Jakubek Y, San Lucas FA, Lang W et al. 2019. Driver mutations in normal airway epithelium elucidate spatiotemporal resolution of lung cancer. Am. J. Respir. Crit. Care Med. 200:742–50
    [Google Scholar]
  52. Kargl J, Busch SE, Yang GH, Kim KH, Hanke ML et al. 2017. Neutrophils dominate the immune cell composition in non-small cell lung cancer. Nat. Commun. 8:14381
    [Google Scholar]
  53. Kathiriya JJ, Brumwell AN, Jackson JR, Tang X, Chapman HA 2020. Distinct airway epithelial stem cells hide among club cells but mobilize to promote alveolar regeneration. Cell Stem Cell 26:346–58.e4
    [Google Scholar]
  54. Kim JH, Kim HS, Kim BJ, Han B, Choi DR, Kwon JH 2018. Prognostic impact of TTF-1 expression in non-squamous non-small-cell lung cancer: a meta-analysis. J. Cancer 9:4279–86
    [Google Scholar]
  55. Kim M, Mun H, Sung CO, Cho EJ, Jeon HJ et al. 2019. Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nat. Commun. 10:3991
    [Google Scholar]
  56. Kitajima S, Ivanova E, Guo S, Yoshida R, Campisi M et al. 2019. Suppression of STING associated with LKB1 loss in KRAS-driven lung cancer. Cancer Discov 9:34–45
    [Google Scholar]
  57. Kortlever RM, Sodir NM, Wilson CH, Burkhart DL, Pellegrinet L et al. 2017. Myc cooperates with Ras by programming inflammation and immune suppression. Cell 171:1301–15.e14
    [Google Scholar]
  58. Kuang M, Shen X, Yuan C, Hu H, Zhang Y et al. 2018. clinical significance of complex glandular patterns in lung adenocarcinoma: clinicopathologic and molecular study in a large series of cases. Am. J. Clin. Pathol. 150:65–73
    [Google Scholar]
  59. Kuo CS, Krasnow MA. 2015. Formation of a neurosensory organ by epithelial cell slithering. Cell 163:394–405
    [Google Scholar]
  60. Labernadie A, Kato T, Brugues A, Serra-Picamal X, Derzsi S et al. 2017. A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion. Nat. Cell Biol. 19:224–37
    [Google Scholar]
  61. Lambrechts D, Wauters E, Boeckx B, Aibar S, Nittner D et al. 2018. Phenotype molding of stromal cells in the lung tumor microenvironment. Nat. Med. 24:1277–89
    [Google Scholar]
  62. Laughney AM, Hu J, Campbell NR, Bakhoum SF, Setty M et al. 2020. Regenerative lineages and immune-mediated pruning in lung cancer metastasis. Nat. Med. 26:259–69
    [Google Scholar]
  63. Lavin Y, Kobayashi S, Leader A, Amir ED, Elefant N et al. 2017. Innate immune landscape in early lung adenocarcinoma by paired single-cell analyses. Cell 169:750–65.e17
    [Google Scholar]
  64. Lawson DA, Kessenbrock K, Davis RT, Pervolarakis N, Werb Z 2018. Tumour heterogeneity and metastasis at single-cell resolution. Nat. Cell Biol. 20:1349–60
    [Google Scholar]
  65. Lázaro S, Pérez-Crespo M, Lorz C, Bernardini A, Oteo M et al. 2019. Differential development of large-cell neuroendocrine or small-cell lung carcinoma upon inactivation of 4 tumor suppressor genes. PNAS 116:22300–6
    [Google Scholar]
  66. LeBoeuf SE, Wu WL, Karakousi TR, Karadal B, Jackson SR et al. 2020. Activation of oxidative stress response in cancer generates a druggable dependency on exogenous non-essential amino acids. Cell Metab 31:339–50.e4
    [Google Scholar]
  67. Lee JJ, Park S, Park H, Kim S, Lee J et al. 2019. Tracing oncogene rearrangements in the mutational history of lung adenocarcinoma. Cell 177:1842–57.e21
    [Google Scholar]
  68. Lee JK, Lee J, Kim S, Kim S, Youk J et al. 2017. Clonal history and genetic predictors of transformation into small-cell carcinomas from lung adenocarcinomas. J. Clin. Oncol. 35:3065–74
    [Google Scholar]
  69. Li CM, Gocheva V, Oudin MJ, Bhutkar A, Wang SY et al. 2015. Foxa2 and Cdx2 cooperate with Nkx2–1 to inhibit lung adenocarcinoma metastasis. Genes Dev 29:1850–62
    [Google Scholar]
  70. Li F, Li Z, Han Q, Cheng Y, Ji W et al. 2020. Enhanced autocrine FGF19/FGFR4 signaling drives the progression of lung squamous cell carcinoma, which responds to mTOR inhibitor AZD2104. Oncogene 39:3507–21
    [Google Scholar]
  71. Lim JS, Ibaseta A, Fischer MM, Cancilla B, O'Young G et al. 2017. Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer. Nature 545:360–64
    [Google Scholar]
  72. Lin C, Song H, Huang C, Yao E, Gacayan R et al. 2012. Alveolar type II cells possess the capability of initiating lung tumor development. PLOS ONE 7:e53817
    [Google Scholar]
  73. Liu A, Sun X, Xu J, Xuan Y, Zhao Y et al. 2020. Relevance and prognostic ability of Twist, Slug and tumor spread through air spaces in lung adenocarcinoma. Cancer Med 9:1986–98
    [Google Scholar]
  74. Liu L, Yang Y, Liu S, Tao T, Cai J et al. 2019. EGF-induced nuclear localization of SHCBP1 activates β-catenin signaling and promotes cancer progression. Oncogene 38:747–64
    [Google Scholar]
  75. Logan CY, Desai TJ. 2015. Keeping it together: Pulmonary alveoli are maintained by a hierarchy of cellular programs. BioEssays 37:1028–37
    [Google Scholar]
  76. Lu Z, Zou J, Li S, Topper MJ, Tao Y et al. 2020. Epigenetic therapy inhibits metastases by disrupting premetastatic niches. Nature 579:284–90
    [Google Scholar]
  77. Mainardi S, Mijimolle N, Francoz S, Vicente-Duenas C, Sanchez-Garcia I, Barbacid M 2014. Identification of cancer initiating cells in K-Ras driven lung adenocarcinoma. PNAS 111:255–60
    [Google Scholar]
  78. Malladi S, Macalinao DG, Jin X, He L, Basnet H et al. 2016. Metastatic latency and immune evasion through autocrine inhibition of WNT. Cell 165:45–60
    [Google Scholar]
  79. Marcoux N, Gettinger SN, O'Kane G, Arbour KC, Neal JW et al. 2019. EGFR-mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: clinical outcomes. J. Clin. Oncol. 37:278–85
    [Google Scholar]
  80. Matsuo Y, Shiomi K, Sonoda D, Mikubo M, Naito M et al. 2018. Molecular alterations in a new cell line (KU-Lu-MPPt3) established from a human lung adenocarcinoma with a micropapillary pattern. J. Cancer Res. Clin. Oncol. 144:75–87
    [Google Scholar]
  81. Mayers JR, Torrence ME, Danai LV, Papagiannakopoulos T, Davidson SM et al. 2016. Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers. Science 353:1161–65
    [Google Scholar]
  82. McFadden DG, Politi K, Bhutkar A, Chen FK, Song X et al. 2016. Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma. PNAS 113:E6409–17
    [Google Scholar]
  83. Mendonsa AM, Na TY, Gumbiner BM 2018. E-cadherin in contact inhibition and cancer. Oncogene 37:4769–80
    [Google Scholar]
  84. Milewski D, Balli D, Ustiyan V, Le T, Dienemann H et al. 2017. FOXM1 activates AGR2 and causes progression of lung adenomas into invasive mucinous adenocarcinomas. PLOS Genet 13:e1007097
    [Google Scholar]
  85. Mitchell KA, Nichols N, Tang W, Walling J, Stevenson H et al. 2019. Recurrent PTPRT/JAK2 mutations in lung adenocarcinoma among African Americans. Nat. Commun. 10:5735
    [Google Scholar]
  86. Mollaoglu G, Jones A, Wait SJ, Mukhopadhyay A, Jeong S et al. 2018. The lineage-defining transcription factors SOX2 and NKX2–1 determine lung cancer cell fate and shape the tumor immune microenvironment. Immunity 49:764–79.e9
    [Google Scholar]
  87. Monterisi S, Lo Riso P, Russo K, Bertalot G, Vecchi M et al. 2018. HOXB7 overexpression in lung cancer is a hallmark of acquired stem-like phenotype. Oncogene 37:3575–88
    [Google Scholar]
  88. Morales Torres C, Wu MY, Hobor S, Wainwright EN, Martin MJ et al. 2020. Selective inhibition of cancer cell self-renewal through a Quisinostat-histone H1.0 axis. Nat. Commun. 11:1792
    [Google Scholar]
  89. Na TY, Schecterson L, Mendonsa AM, Gumbiner BM 2020. The functional activity of E-cadherin controls tumor cell metastasis at multiple steps. PNAS 117:5931–37
    [Google Scholar]
  90. Nabhan A, Brownfield DG, Harbury PB, Krasnow MA, Desai TJ 2018. Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells. Science 359:1118–23
    [Google Scholar]
  91. Nagendran M, Riordan DP, Harbury PB, Desai TJ 2018. Automated cell type classification in intact tissues by single-cell molecular profiling. eLife 7:e30510
    [Google Scholar]
  92. Nahar R, Zhai W, Zhang T, Takano A, Khng AJ et al. 2018. Elucidating the genomic architecture of Asian EGFR-mutant lung adenocarcinoma through multi-region exome sequencing. Nat. Commun. 9:216
    [Google Scholar]
  93. Okubo T, Hogan BL. 2004. Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm. J. Biol. 3:11
    [Google Scholar]
  94. Omori T, Aokage K, Nakamura H, Katsumata S, Miyoshi T et al. 2019. Growth patterns of small peripheral squamous cell carcinoma of the lung and their impacts on pathological and biological characteristics of tumor cells. J. Cancer Res. Clin. Oncol. 145:1773–83
    [Google Scholar]
  95. Oser MG, Sabet AH, Gao W, Chakraborty AA, Schinzel AC et al. 2019. The KDM5A/RBP2 histone demethylase represses NOTCH signaling to sustain neuroendocrine differentiation and promote small cell lung cancer tumorigenesis. Genes Dev 33:1718–38
    [Google Scholar]
  96. Ostrin EJ, Little DR, Gerner-Mauro KN, Sumner EA, Rios-Corzo R et al. 2018. β-Catenin maintains lung epithelial progenitors after lung specification. Development 145:dev160788
    [Google Scholar]
  97. Ouadah Y, Rojas ER, Riordan DP, Capostagno S, Kuo CS, Krasnow MA 2019. Rare pulmonary neuroendocrine cells are stem cells regulated by Rb, p53, and Notch. Cell 179:403–16.e23
    [Google Scholar]
  98. Padmanaban V, Krol I, Suhail Y, Szczerba BM, Aceto N et al. 2019. E-cadherin is required for metastasis in multiple models of breast cancer. Nature 573:439–44
    [Google Scholar]
  99. Park JW, Lee JK, Sheu KM, Wang L, Balanis NG et al. 2018. Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage. Science 362:91–95
    [Google Scholar]
  100. PCAWG (Pan-Cancer Anal. Whole Genomes) Consort 2020. Pan-cancer analysis of whole genomes. Nature 578:82–93
    [Google Scholar]
  101. Petljak M, Alexandrov LB, Brammeld JS, Price S, Wedge DC et al. 2019. Characterizing mutational signatures in human cancer cell lines reveals episodic APOBEC mutagenesis. Cell 176:1282–94.e20
    [Google Scholar]
  102. Polak P, Karlic R, Koren A, Thurman R, Sandstrom R et al. 2015. Cell-of-origin chromatin organization shapes the mutational landscape of cancer. Nature 518:360–64
    [Google Scholar]
  103. Qian J, Zhao S, Zou Y, Rahman SMJ, Senosain MF et al. 2020. Genomic underpinnings of tumor behavior in in situ and early lung adenocarcinoma. Am. J. Respir. Crit. Care Med. 201:697–706
    [Google Scholar]
  104. Raoof S, Mulford IJ, Frisco-Cabanos H, Nangia V, Timonina D et al. 2019. Targeting FGFR overcomes EMT-mediated resistance in EGFR mutant non-small cell lung cancer. Oncogene 38:6399–413
    [Google Scholar]
  105. Ray S, Chiba N, Yao C, Guan X, McConnell AM et al. 2016. Rare SOX2+ airway progenitor cells generate KRT5+ cells that repopulate damaged alveolar parenchyma following influenza virus infection. Stem Cell Reports 7:817–25
    [Google Scholar]
  106. Ricaurte LM, Arrieta O, Zatarain-Barron ZL, Cardona AF 2018. Comprehensive review of fetal adenocarcinoma of the lung. Lung Cancer 9:57–63
    [Google Scholar]
  107. Ridker PM, MacFadyen JG, Thuren T, Everett BM, Libby P, Glynn RJ 2017. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet 390:1833–42
    [Google Scholar]
  108. Rogers ZN, McFarland CD, Winters IP, Seoane JA, Brady JJ et al. 2018. Mapping the in vivo fitness landscape of lung adenocarcinoma tumor suppression in mice. Nat. Genet. 50:483–86
    [Google Scholar]
  109. Rosenthal R, Cadieux EL, Salgado R, Bakir MA, Moore DA et al. 2019. Neoantigen-directed immune escape in lung cancer evolution. Nature 567:479–85
    [Google Scholar]
  110. Rudin CM, Poirier JT, Byers LA, Dive C, Dowlati A et al. 2019. Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data. Nat. Rev. Cancer 19:289–97
    [Google Scholar]
  111. Ruiz Garcia S, Deprez M, Lebrigand K, Cavard A, Paquet A et al. 2019. Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures. Development 146:dev177428
    [Google Scholar]
  112. Sahai E, Astsaturov I, Cukierman E, DeNardo DG, Egeblad M et al. 2020. A framework for advancing our understanding of cancer-associated fibroblasts. Nat. Rev. Cancer 20:174–86
    [Google Scholar]
  113. Salahudeen AA, Choi SS, Rustagi A, Zhu J, van Unen et al. 2020. Progenitor identification and SARS-CoV-2 infection in human distal lung organoids. Nature. 588670–75
  114. Sato T, Yoo S, Kong R, Sinha A, Chandramani-Shivalingappa P et al. 2019. Epigenomic profiling discovers trans-lineage SOX2 partnerships driving tumor heterogeneity in lung squamous cell carcinoma. Cancer Res 79:6084–100
    [Google Scholar]
  115. Schmid A, Sailland J, Novak L, Baumlin N, Fregien N, Salathe M 2017. Modulation of Wnt signaling is essential for the differentiation of ciliated epithelial cells in human airways. FEBS Lett 591:3493–506
    [Google Scholar]
  116. Schoenfelder S, Fraser P. 2019. Long-range enhancer-promoter contacts in gene expression control. Nat. Rev. Genet. 20:437–55
    [Google Scholar]
  117. Sekine S, Shibata T, Matsuno Y, Maeshima A, Ishii G et al. 2003. β-Catenin mutations in pulmonary blastomas: association with morule formation. J. Pathol. 200:214–21
    [Google Scholar]
  118. Shiono S, Endo M, Suzuki K, Hayasaka K, Yanagawa N 2019. Spread through air spaces in lung cancer patients is a risk factor for pulmonary metastasis after surgery. J. Thorac. Dis. 11:177–87
    [Google Scholar]
  119. Shirley JL, de Jong YP, Terhorst C, Herzog RW 2020. Immune responses to viral gene therapy vectors. Mol. Ther. 28:709–22
    [Google Scholar]
  120. Singhal S, Stadanlick J, Annunziata MJ, Rao AS, Bhojnagarwala PS et al. 2019. Human tumor-associated monocytes/macrophages and their regulation of T cell responses in early-stage lung cancer. Sci. Transl. Med. 11:eaat1500
    [Google Scholar]
  121. Sinkevicius KW, Bellaria KJ, Barrios J, Pessina P, Gupta M et al. 2018. E-cadherin loss accelerates tumor progression and metastasis in a mouse model of lung adenocarcinoma. Am. J. Respir. Cell Mol. Biol. 59:237–45
    [Google Scholar]
  122. Skoulidis F, Byers LA, Diao L, Papadimitrakopoulou VA, Tong P et al. 2015. Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities. Cancer Discov 5:860–77
    [Google Scholar]
  123. Stewart CA, Gay CM, Xi Y, Sivajothi S, Sivakamasundari V et al. 2020. Single-cell analyses reveal increased intratumoral heterogeneity after the onset of therapy resistance in small-cell lung cancer. Nat. Cancer 1:423–36
    [Google Scholar]
  124. Tamanini A, Nicolis E, Bonizzato A, Bezzerri V, Melotti P et al. 2006. Interaction of adenovirus type 5 fiber with the coxsackievirus and adenovirus receptor activates inflammatory response in human respiratory cells. J. Virol. 80:11241–54
    [Google Scholar]
  125. Tammela T, Sanchez-Rivera FJ, Cetinbas NM, Wu K, Joshi NS et al. 2017. A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma. Nature 545:355–59
    [Google Scholar]
  126. Tata PR, Chow RD, Saladi SV, Tata A, Konkimalla A et al. 2018. Developmental history provides a roadmap for the emergence of tumor plasticity. Dev. Cell 44:679–93.e5
    [Google Scholar]
  127. Teixeira VH, Pipinikas CP, Pennycuick A, Lee-Six H, Chandrasekharan D et al. 2019. Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions. Nat. Med. 25:517–25
    [Google Scholar]
  128. Teramoto M, Sugawara R, Minegishi K, Uchikawa M, Takemoto T et al. 2020. The absence of SOX2 in the anterior foregut alters the esophagus into trachea and bronchi in both epithelial and mesenchymal components. Biol. Open 9:bio048728
    [Google Scholar]
  129. Tippimanchai DD, Nolan K, Poczobutt J, Verzosa G, Li H et al. 2018. Adenoviral vectors transduce alveolar macrophages in lung cancer models. OncoImmunology 7:e1438105
    [Google Scholar]
  130. Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR et al. 2011. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J. Thorac. Oncol. 6:244–85
    [Google Scholar]
  131. Treutlein B, Brownfield DG, Wu AR, Neff NF, Mantalas GL et al. 2014. Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq. Nature 509:371–75
    [Google Scholar]
  132. van Veen JE, Scherzer M, Boshuizen J, Chu M, Liu A et al. 2019. Mutationally-activated PI3′-kinase-α promotes de-differentiation of lung tumors initiated by the BRAFV600E oncoprotein kinase. eLife 8:e43668
    [Google Scholar]
  133. Vaughan AE, Brumwell AN, Xi Y, Gotts JE, Brownfield DG et al. 2015. Lineage-negative progenitors mobilize to regenerate lung epithelium after major injury. Nature 517:621–25
    [Google Scholar]
  134. Wang K, Ji W, Yu Y, Li Z, Niu X et al. 2018. FGFR1-ERK1/2-SOX2 axis promotes cell proliferation, epithelial–mesenchymal transition, and metastasis in FGFR1-amplified lung cancer. Oncogene 37:5340–54
    [Google Scholar]
  135. Weeden CE, Chen Y, Ma SB, Hu Y, Ramm G et al. 2017. Lung basal stem cells rapidly repair DNA damage using the error-prone nonhomologous end-joining pathway. PLOS Biol 15:e2000731
    [Google Scholar]
  136. Williams ED, Gao D, Redfern A, Thompson EW 2019. Controversies around epithelial–mesenchymal plasticity in cancer metastasis. Nat. Rev. Cancer 19:716–32
    [Google Scholar]
  137. Wooten DJ, Groves SM, Tyson DR, Liu Q, Lim JS et al. 2019. Systems-level network modeling of small cell lung cancer subtypes identifies master regulators and destabilizers. PLOS Comput. Biol. 15:e1007343
    [Google Scholar]
  138. Xu X, Rock JR, Lu Y, Futtner C, Schwab B et al. 2012. Evidence for type II cells as cells of origin of K-Ras–induced distal lung adenocarcinoma. PNAS 109:4910–15
    [Google Scholar]
  139. Yang D, Qu F, Cai H, Chuang CH, Lim JS et al. 2019. Axon-like protrusions promote small cell lung cancer migration and metastasis. eLife 8:e50616
    [Google Scholar]
  140. Yang Y, Riccio P, Schotsaert M, Mori M, Lu J et al. 2018. Spatial-temporal lineage restrictions of embryonic p63+ progenitors establish distinct stem cell pools in adult airways. Dev. Cell 44:752–61.e4
    [Google Scholar]
  141. Yao E, Lin C, Wu Q, Zhang K, Song H, Chuang PT 2018. Notch signaling controls transdifferentiation of pulmonary neuroendocrine cells in response to lung injury. Stem Cells 36:377–91
    [Google Scholar]
  142. Yao S, Huang HY, Han X, Ye Y, Qin Z et al. 2019. Keratin 14-high subpopulation mediates lung cancer metastasis potentially through Gkn1 upregulation. Oncogene 38:6354–69
    [Google Scholar]
  143. Yizhak K, Aguet F, Kim J, Hess JM, Kubler K et al. 2019. RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues. Science 364:eaaw0726
    [Google Scholar]
  144. Yoshida K, Gowers KHC, Lee-Six H, Chandrasekharan DP, Coorens T et al. 2020. Tobacco smoking and somatic mutations in human bronchial epithelium. Nature 578:266–72
    [Google Scholar]
  145. Zacharias WJ, Frank DB, Zepp JA, Morley MP, Alkhaleel FA et al. 2018. Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor. Nature 555:251–55
    [Google Scholar]
  146. Zhang H, Fillmore Brainson C, Koyama S, Redig AJ, Chen T et al. 2017. Lkb1 inactivation drives lung cancer lineage switching governed by polycomb repressive complex 2. Nat. Commun. 8:14922
    [Google Scholar]
  147. Zhang J, Sun J, Liang XL, Lu JL, Luo YF, Liang ZY 2017. Differences between low and high grade fetal adenocarcinoma of the lung: a clinicopathological and molecular study. J. Thorac. Dis. 9:2071–78
    [Google Scholar]
  148. Zhang Z, Hunter L, Wu G, Maidstone R, Mizoro Y et al. 2019. Genome-wide effect of pulmonary airway epithelial cell-specific Bmal1 deletion. FASEB J 33:6226–38
    [Google Scholar]
  149. Zhang Z, Newton K, Kummerfeld SK, Webster J, Kirkpatrick DS et al. 2017. Transcription factor Etv5 is essential for the maintenance of alveolar type II cells. PNAS 114:3903–8
    [Google Scholar]
  150. Zhou B, Flodby P, Luo J, Castillo DR, Liu Y et al. 2018. Claudin-18-mediated YAP activity regulates lung stem and progenitor cell homeostasis and tumorigenesis. J. Clin. Investig. 128:970–84
    [Google Scholar]
/content/journals/10.1146/annurev-cancerbio-070820-032858
Loading
  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error