• Aday S, Cecchelli R, Hallier‐Vanuxeem D, Dehouck MP, Ferreira L (2016) Stem cell‐based human blood‐brain barrier models for drug discovery and delivery. Trends Biotechnol 34: 382–393

    Google Scholar 

  • Aggarwal C, Wang X, Ranganathan A, Torigian D, Troxel A, Evans T, Cohen RB, Vaidya B, Rao C, Connelly M et al (2017) Circulating tumor cells as a predictive biomarker in patients with small cell lung cancer undergoing chemotherapy. Lung Cancer 112: 118–125

    Google Scholar 

  • Akoun GM, Scarna HM, Milleron BJ, Bénichou MP, Herman DP (1985) Serum neuron‐specific enolase. A marker for disease extent and response to therapy for small‐cell lung cancer. Chest 87: 39–43

    Google Scholar 

  • Antonia SJ, López‐Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jäger D, Pietanza MC, Le DT, de Braud F et al (2016) Nivolumab alone and nivolumab plus ipilimumab in recurrent small‐cell lung cancer (CheckMate 032): a multicentre, open‐label, phase 1/2 trial. Lancet Oncol 17: 883–895

    Google Scholar 

  • Aupérin A, Arriagada R, Pignon J‐P, Le Péchoux C, Gregor A, Stephens RJ, Kristjansen PEG, Johnson BE, Ueoka H, Wagner H et al (1999) Prophylactic cranial irradiation for patients with small‐cell lung cancer in complete remission. N Engl J Med 341: 476–484

    Google Scholar 

  • Barnes H, See K, Barnett S, Manser R (2017) Surgery for limited‐stage small‐cell lung cancer. Cochrane Database Syst Rev 4: CD011917

  • Best SA, Hess JB, Souza‐Fonseca‐Guimaraes F, Cursons J, Kersbergen A, Dong X, Rautela J, Hyslop SR, Ritchie ME, Davis MJ et al (2020) Harnessing natural killer immunity in metastatic SCLC. J Thorac Oncol 15: 1507–1521

    Google Scholar 

  • Böttger F, Semenova EA, Song JY, Ferone G, van der Vliet J, Cozijnsen M, Bhaskaran R, Bombardelli L, Piersma SR, Pham TV et al (2019) Tumor heterogeneity underlies differential cisplatin sensitivity in mouse models of small‐cell lung cancer. Cell Rep 27: 3345–3358.e4

    Google Scholar 

  • Burger M, Glodek A, Hartmann T, Schmitt‐Gräff A, Silberstein LE, Fujii N, Kipps TJ, Burger JA (2003) Functional expression of CXCR4 (CD184) on small‐cell lung cancer cells mediates migration, integrin activation, and adhesion to stromal cells. Oncogene 22: 8093–8101

    Google Scholar 

  • Bütof R, Gumina C, Valentini C, Sommerer A, Appold S, Zips D, Löck S, Baumann M, Troost EGC (2017) Sites of recurrent disease and prognostic factors in SCLC patients treated with radiochemotherapy. Clin Transl Radiat Oncol 7: 36–42

    Google Scholar 

  • Byers LA, Rudin CM (2015) Small cell lung cancer: Where do we go from here? Cancer 121: 664–672

    Google Scholar 

  • Calbo J, van Montfort E, Proost N, van Drunen E, Beverloo HB, Meuwissen R, Berns A (2011) A functional role for tumor cell heterogeneity in a mouse model of small cell lung cancer. Cancer Cell 19: 244–256

    Google Scholar 

  • Carney DN, Gazdar AF, Bepler G, Guccion JG, Marangos PJ, Moody TW, Zweig MH, Minna JD (1985) Establishment and identification of small cell lung cancer cell lines having classic and variant features. Cancer Res 45: 2913–2923

    Google Scholar 

  • Carter L, Rothwell DG, Mesquita B, Smowton C, Leong HS, Fernandez‐Gutierrez F, Li Y, Burt DJ, Antonello J, Morrow CJ et al (2017) Molecular analysis of circulating tumor cells identifies distinct copy‐number profiles in patients with chemosensitive and chemorefractory small‐cell lung cancer. Nat Med 23: 114–119

    Google Scholar 

  • de Castro Carpeño J, Dols MC, Gomez MD, Gracia PR, Crama L, Campelo MRG (2019) Survival outcomes in stage IV small‐cell lung cancer (IV‐SCLC): Analysis from SEER database. Ann Oncol 30: xi30

    Google Scholar 

  • Chaffer CL, San Juan BP, Lim E, Weinberg RA (2016) EMT, cell plasticity and metastasis. Cancer Metastasis Rev 35: 645–654

    Google Scholar 

  • Chang MH, Lee K, Lee KY, Kim YS, Kim YK, Kang JH (2012) Prognostic role of integrin β 1, E‐cadherin, and rac1 expression in small cell lung cancer. APMIS 120: 28–38

    Google Scholar 

  • Chung HC, Piha‐Paul SA, Lopez‐Martin J, Schellens JHM, Kao S, Miller WH, Delord JP, Gao B, Planchard D, Gottfried M et al (2020) Pembrolizumab after two or more lines of previous therapy in patients with recurrent or metastatic SCLC: results from the KEYNOTE‐028 and KEYNOTE‐158 studies. J Thorac Oncol 15: 618–627

    Google Scholar 

  • Cui M, Augert A, Rongione M, Conkrite K, Parazzoli S, Nikitin AY, Ingolia N, MacPherson D (2014) PTEN is a potent suppressor of small cell lung cancer. Mol Cancer Res 12: 654–659

    Google Scholar 

  • Dammert MA, Brägelmann J, Olsen RR, Böhm S, Monhasery N, Whitney CP, Chalishazar MD, Tumbrink HL, Guthrie MR, Klein S et al (2019) MYC paralog‐dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer. Nat Commun 10: 3485

    Google Scholar 

  • Denny SK, Yang D, Chuang C‐H, Brady JJ, Lim JS, Grüner BM, Chiou S‐H, Schep AN, Baral J, Hamard CC et al (2016) Nfib promotes metastasis through a widespread increase in chromatin accessibility. Cell 166: 328–342

    Google Scholar 

  • Dillekås H, Rogers MS, Straume O (2019) Are 90% of deaths from cancer caused by metastases? Cancer Med 8: 5574–5576

    Google Scholar 

  • Dooley AL, Winslow MM, Chiang DY, Banerji S, Stransky N, Dayton TL, Snyder EL, Senna S, Whittaker CA, Bronson RT et al (2011) Nuclear factor I/B is an oncogene in small cell lung cancer. Genes Dev 25: 1470–1475

    Google Scholar 

  • Drapkin BJ, George J, Christensen CL, Mino‐Kenudson M, Dries R, Sundaresan T, Phat S, Myers DT, Zhong J, Igo P et al (2018) Genomic and functional fidelity of small cell lung cancer patient‐derived xenografts. Cancer Discov 8: 600–615

    Google Scholar 

  • Feldman LE, Shin KC, Natale RB, Todd RF (1991) B1 integrin expression on human small cell lung cancer cells. Cancer Res 51: 1065–1070

    Google Scholar 

  • Ferone G, Lee MC, Sage J, Berns A (2020) Cells of origin of lung cancers: lessons from mouse studies. Genes Dev 34: 1017–1032

    Google Scholar 

  • Fox W, Scadding JG (1973) Medical Research Council comparative trial of surgery and radiotherapy for primary treatment of small‐celled or oat‐celled carcinoma of bronchus. Ten‐year follow‐up. Lancet 302: 63–65

    Google Scholar 

  • Froudarakis ME (2012) Pleural effusion in lung cancer: more questions than answers. Respiration 83: 367–376

    Google Scholar 

  • Furuta M, Kikuchi H, Shoji T, Takashima Y, Kikuchi E, Kikuchi J, Kinoshita I, Dosaka‐Akita H, Sakakibara‐Konishi J (2019) DLL3 regulates the migration and invasion of small cell lung cancer by modulating Snail. Cancer Sci 110: 1599–1608

    Google Scholar 

  • Gardner EE, Lok BH, Schneeberger VE, Desmeules P, Miles LA, Arnold PK, Ni A, Khodos I, de Stanchina E, Nguyen T et al (2017) Chemosensitive relapse in small cell lung cancer proceeds through an EZH2‐SLFN11 axis. Cancer Cell 31: 286–299

    Google Scholar 

  • Gazdar AF, Carney DN, Nau MM, Minna JD (1985) Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological, and growth properties. Cancer Res 45: 2924–2930

    Google Scholar 

  • Gazdar AF, Savage TK, Johnson JE, Berns A, Sage J, Linnoila RI, Macpherson D, Mcfadden DG, Farago A, Jacks T et al (2015) The comparative pathology of genetically engineered mouse models for neuroendocrine carcinomas of the lung. J Thorac Oncol 10: 553–564

    Google Scholar 

  • Gazdar AF, Bunn PA, Minna JD (2017) Small‐cell lung cancer: what we know, what we need to know and the path forward. Nat Rev Cancer 17: 725–737

    Google Scholar 

  • Geminder H, Sagi‐Assif O, Goldberg L, Meshel T, Rechavi G, Witz IP, Ben‐Baruch A (2001) A possible role for CXCR4 and its ligand, the CXC chemokine stromal cell‐derived factor‐1, in the development of bone marrow metastases in neuroblastoma. J Immunol 167: 4747–4757

    Google Scholar 

  • George J, Lim JS, Jang SJ, Cun Y, Ozretia L, Kong G, Leenders F, Lu X, Fernández‐Cuesta L, Bosco G et al (2015) Comprehensive genomic profiles of small cell lung cancer. Nature 524: 47–53

    Google Scholar 

  • Gupta GP, Massagué J (2006) Cancer metastasis: building a framework. Cell 127: 679–695

    Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144: 646–674

    Google Scholar 

  • Harbour JW, Lai SL, Whang‐Peng J, Gazdar AF, Minna JD, Kaye FJ (1988) Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science (80‐) 241: 353–357

    Google Scholar 

  • Hartmann TN, Burger JA, Glodek A, Fujii N, Burger M (2005) CXCR4 chemokine receptor and integrin signaling co‐operate in mediating adhesion and chemoresistance in small cell lung cancer (SCLC) cells. Oncogene 24: 4462–4471

    Google Scholar 

  • Hassan WA, Yoshida R, Kudoh S, Hasegawa K, Niimori‐Kita K, Ito T (2014) Notch1 controls cell invasion and metastasis in small cell lung carcinoma cell lines. Lung Cancer 86: 304–310

    Google Scholar 

  • He S, Roberts PJ, Sorrentino JA, Bisi JE, Storrie‐White H, Tiessen RG, Makhuli KM, Wargin WA, Tadema H, Van Hoogdalem EJ et al (2017) Transient CDK4/6 inhibition protects hematopoietic stem cells from chemotherapy‐induced exhaustion. Sci Transl Med 9: eaal3986

    Google Scholar 

  • Heidemann F, Schildt A, Schmid K, Bruns OT, Riecken K, Jung C, Ittrich H, Wicklein D, Reimer R, Fehse B et al (2014) Selectins mediate small cell lung cancer systemic metastasis. PLoS One 9: e92327

    Google Scholar 

  • Hipp S, Voynov V, Drobits‐Handl B, Giragossian C, Trapani F, Nixon AE, Scheer JM, Adam PJ (2020) A bispecific DLL3/CD3 IgG‐like T‐cell engaging antibody induces antitumor responses in small cell lung cancer. Clin. Cancer Res 26: 5258–5268

    Google Scholar 

  • Hodgkinson CL, Morrow CJ, Li Y, Metcalf RL, Rothwell DG, Trapani F, Polanski R, Burt DJ, Simpson KL, Morris K et al (2014) Tumorigenicity and genetic profiling of circulating tumor cells in small‐cell lung cancer. Nat Med 20: 897–903

    Google Scholar 

  • Horn L, Mansfield AS, Szczȩsna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M et al (2018) First‐line atezolizumab plus chemotherapy in extensive‐stage small‐cell lung cancer. N Engl J Med 379: 2220–2229

    Google Scholar 

  • Hosseini H, Obradovic MMS, Hoffmann M, Harper KL, Sosa MS, Werner‐Klein M, Nanduri LK, Werno C, Ehrl C, Maneck M et al (2016) Early dissemination seeds metastasis in breast cancer. Nature 540: 552–558

    Google Scholar 

  • Hou JM, Krebs MG, Lancashire L, Sloane R, Backen A, Swain RK, Priest LJC, Greystoke A, Zhou C, Morris K et al (2012) Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small‐cell lung cancer. J Clin Oncol 30: 525–532

    Google Scholar 

  • Howlader N, Forjaz G, Mooradian MJ, Meza R, Kong CY, Cronin KA, Mariotto AB, Lowy DR, Feuer EJ (2020) The effect of advances in lung‐cancer treatment on population mortality. N Engl J Med 383: 640–649

    Google Scholar 

  • Hu Z, Ding J, Ma Z, Sun R, Seoane JA, Shaffer JS, Suarez CJ, Berghoff AS, Cremolini C, Falcone A et al (2019) Quantitative evidence for early metastatic seeding in colorectal cancer. Nat Genet 51: 1113–1122

    Google Scholar 

  • Hung CS, Su HY, Liang HH, Lai CW, Chang YC, Ho YS, Wu CH, Ho JD, Wei PL, Chang YJ (2014) High‐level expression of CXCR4 in breast cancer is associated with early distant and bone metastases. Tumor Biol 35: 1581–1588

    Google Scholar 

  • Huang YH, Klingbeil O, He XY, Wu XS, Arun G, Lu B, Somerville TDD, Milazzo JP, Wilkinson JE, Demerdash OE et al (2018) POU2F3 is a master regulator of a tuft cell‐like variant of small cell lung cancer. Genes Dev 32: 915–928

    Google Scholar 

  • Huang J, Cao D, Sha J, Zhu X, Han S (2019) DLL3 is regulated by LIN28B and miR‐518d‐5p and regulates cell proliferation, migration and chemotherapy response in advanced small cell lung cancer. Biochem Biophys Res Commun 514: 853–860

    Google Scholar 

  • Ilhan‐Mutlu A, Siehs C, Berghoff AS, Ricken G, Widhalm G, Wagner L, Preusser M (2016) Expression profiling of angiogenesis‐related genes in brain metastases of lung cancer and melanoma. Tumor Biol 37: 1173–1182

    Google Scholar 

  • Ireland AS, Micinski AM, Kastner DW, Guo B, Wait SJ, Spainhower KB, Conley CC, Chen OS, Guthrie MR, Soltero D et al (2020) MYC drives temporal evolution of small cell lung cancer subtypes by reprogramming neuroendocrine fate. Cancer Cell 38: 60–78.e12

    Google Scholar 

  • Jacoby JJ, Erez B, Korshunova MV, Williams RR, Furutani K, Takahashi O, Kirkpatrick L, Lippman SM, Powis G, O’Reilly MS et al (2010) Treatment with hif‐1α antagonist PX‐478 inhibits progression and spread of orthotopic human small cell lung cancer and lung adenocarcinoma in mice. J Thorac Oncol 5: 940–949

    Google Scholar 

  • Jia D, Augert A, Kim DW, Eastwood E, Wu N, Ibrahim AH, Kim KB, Dunn CT, Pillai SPS, Gazdar AF et al (2018) Crebbp loss drives small cell lung cancer and increases sensitivity to HDAC inhibition. Cancer Discov 8: 1422–1437

    Google Scholar 

  • Jørgensen LGM, Østerlind K, Genollá J, Gomm SA, Hernández JR, Johnson PWM, Løber J, Splinter TAW, Szturmowicz M (1996) Serum neuron‐specific enolase (S‐NSE) and the prognosis in small‐cell lung cancer (SCLC): a combined multivariable analysis on data from nine centres. Br J Cancer 74: 463–467

    Google Scholar 

  • Kanemoto K, Satoh H, Ishikawa H, Sekizawa K (2006) Neurone‐specific enolase and liver metastasis in small cell lung cancer. Clin Oncol 18: 505

    Google Scholar 

  • Kawasaki K, Toshimitsu K, Matano M, Fujita M, Fujii M, Togasaki K, Ebisudani T, Shimokawa M, Takano A, Takahashi S et al (2020) An organoid biobank of neuroendocrine neoplasms enables genotype‐phenotype mapping. Cell 5: 1420–1435

    Google Scholar 

  • Kitamura T, Qian BZ, Pollard JW (2015) Immune cell promotion of metastasis. Nat Rev Immunol 15: 73–86

    Google Scholar 

  • Kuo CS, Krasnow MA (2015) Formation of a neurosensory organ by epithelial cell slithering. Cell 163: 394–405

    Google Scholar 

  • Kwon MC, Proost N, Song JY, Sutherland KD, Zevenhoven J, Berns A (2015) Paracrine signaling between tumor subclones of mouse sclc: a critical role of ets transcription factor pea3 in facilitating metastasis. Genes Dev 29: 1587–1592

    Google Scholar 

  • Lai AY, Sorrentino JA, Dragnev KH, Weiss JM, Owonikoko TK, Rytlewski JA, Hood J, Yang Z, Malik RK, Strum JC et al (2020) CDK4/6 inhibition enhances antitumor efficacy of chemotherapy and immune checkpoint inhibitor combinations in preclinical models and enhances T‐cell activation in patients with SCLC receiving chemotherapy. J Immunother Cancer 8: e000847

    Google Scholar 

  • Lallo A, Gulati S, Schenk MW, Khandelwal G, Berglund UW, Pateras IS, Chester CPE, Pham TM, Kalderen C, Frese KK et al (2019) Ex vivo culture of cells derived from circulating tumour cell xenograft to support small cell lung cancer research and experimental therapeutics. Br J Pharmacol 176: 436–450

    Google Scholar 

  • Lambert AW, Pattabiraman DR, Weinberg RA (2017) Emerging biological principles of metastasis. Cell 168: 670–691

    Google Scholar 

  • Li B, Zhao WD, Tan ZM, Fang WG, Zhu L, Chen YH (2006) Involvement of Rho/ROCK signalling in small cell lung cancer migration through human brain microvascular endothelial cells. FEBS Lett 580: 4252–4260

    Google Scholar 

  • Li N, Zhang JP, Guo S, Min J, Liu LL, Su HC, Feng YM, Zhang HL (2012) Down‐regulation of β3‐integrin inhibits bone metastasis of small cell lung cancer. Mol Biol Rep 39: 3029–3035

    Google Scholar 

  • Li B, Wang C, Zhang Y, Zhao XY, Huang B, Wu PF, Li Q, Li H, Liu YS, Cao LY et al (2013) Elevated PLGF contributes to small‐cell lung cancer brain metastasis. Oncogene 32: 2952–2962

    Google Scholar 

  • Li XX, Li RJ, Zhao LJ, Liu NB, Wang P (2015) Expression of molecular factors correlated with metastasis in small cell lung cancer and their significance. Int J Clin Exp Pathol 8: 14676–14684

    Google Scholar 

  • Lim JS, Ibaseta A, Fischer MM, Cancilla B, O’Young G, Cristea S, Luca VC, Yang Di, Jahchan NS, Hamard C et al (2017) Intratumoural heterogeneity generated by Notch signalling promotes small‐cell lung cancer. Nature 545: 360–364

    Google Scholar 

  • Lukas RV, Gondi V, Kamson DO, Kumthekar P, Salgia R (2017) State‐of‐the‐art considerations in small cell lung cancer brain metastases. Oncotarget 8: 71223–71233

    Google Scholar 

  • Ma N, Pang H, Shen W, Zhang F, Cui Z, Wang J, Wang J, Liu L, Zhang H (2015) Downregulation of CXCR4 by SDF‐KDEL in SBC‐5 cells inhibits their migration in vitro and organ metastasis in vivo. Int J Mol Med 35: 425–432

    Google Scholar 

  • McFadden DG, Papagiannakopoulos T, Taylor‐Weiner A, Stewart C, Carter SL, Cibulskis K, Bhutkar A, McKenna A, Dooley A, Vernon A et al (2014) Genetic and clonal dissection of murine small cell lung carcinoma progression by genome sequencing. Cell 156: 1298–1311

    Google Scholar 

  • Messaritakis I, Nikolaou M, Koinis F, Politaki E, Koutsopoulos A, Lagoudaki E, Vetsika EK, Georgoulias V, Kotsakis A (2019) Characterization of DLL3‐positive circulating tumor cells (CTCs) in patients with small cell lung cancer (SCLC) and evaluation of their clinical relevance during front‐line treatment. Lung Cancer 135: 33–39

    Google Scholar 

  • Meuwissen R, Linn SC, Linnoila RI, Zevenhoven J, Mooi WJ, Berns A (2003) Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell 4: 181–189

    Google Scholar 

  • Miki T, Yano S, Hanibuchi M, Sone S (2000) Bone metastasis model with multiorgan dissemination of human small‐cell lung cancer (SBC‐5) cells in natural killer cell‐depleted SCID mice. Oncol Res 12: 209–217

    Google Scholar 

  • Miller AB, Fox W, Tall R (1969) Five‐year follow‐up of the Medical Research Council comparative trial of surgery and radiotherapy for the primary treatment of small‐celled or oat‐celled carcinoma of the bronchus. Lancet 294: 501–505

    Google Scholar 

  • Mollaoglu G, Guthrie MR, Böhm S, Brägelmann J, Can I, Ballieu PM, Marx A, George J, Heinen C, Chalishazar MD et al (2017) MYC drives progression of small cell lung cancer to a variant neuroendocrine subtype with vulnerability to aurora kinase inhibition. Cancer Cell 31: 270–285

    Google Scholar 

  • Morgensztern D, Besse B, Greillier L, Santana‐Davila R, Ready N, Hann CL, Glisson BS, Farago AF, Dowlati A, Rudin CM et al (2019) Efficacy and safety of rovalpituzumab tesirine in third‐line and beyond patients with DLL3‐expressing, relapsed/refractory small‐cell lung cancer: Results from the phase II TrINITY study. Clin Cancer Res 25: 6958–6966

    Google Scholar 

  • Mousavi A (2020) CXCL12/CXCR4 signal transduction in diseases and its molecular approaches in targeted‐therapy. Immunol Lett 217: 91–115

    Google Scholar 

  • Nakazawa K, Kurishima K, Tamura T, Kagohashi K, Ishikawa H, Hiroaki S, Hizawa N (2012) Specific organ metastases and survival in small cell lung cancer. Oncol Lett 4: 617–620

    Google Scholar 

  • Nguyen DX, Massagué J (2007) Genetic determinants of cancer metastasis. Nat Rev Genet 8: 341–352

    Google Scholar 

  • Nguyen DX, Bos PD, Massagué J (2009) Metastasis: from dissemination to organ‐specific colonization. Nat Rev Cancer 9: 274–284

    Google Scholar 

  • O’Brown NM, Pfau SJ, Gu C (2018) Bridging barriers: A comparative look at the blood‐brain barrier across organisms. Genes Dev 32: 466–478

    Google Scholar 

  • Obermayr E, Agreiter C, Schuster E, Fabikan H, Weinlinger C, Baluchova K, Hamilton G, Hochmair M, Zeillinger R (2019) Molecular characterization of circulating tumor cells enriched by a microfluidic platform in patients with small‐cell lung cancer. Cells 8: 880

    Google Scholar 

  • Onganer PU, Seckl MJ, Djamgoz MBA (2005) Neuronal characteristics of small‐cell lung cancer. Br J Cancer 93: 1197–1201

    Google Scholar 

  • Oshita F, Kameda Y, Hamanaka N, Saito H, Yamada K, Noda K, Mitsuda A (2004) High expression of integrin β1 and p53 is a greater poor prognostic factor than clinical stage in small‐cell lung cancer. Am J Clin Oncol Cancer Clin Trials 27: 215–219

    Google Scholar 

  • Ready NE, Ott PA, Hellmann MD, Zugazagoitia J, Hann CL, de Braud F, Antonia SJ, Ascierto PA, Moreno V, Atmaca A et al (2020) Nivolumab monotherapy and nivolumab plus ipilimumab in recurrent small cell lung cancer: results from the CheckMate 032 randomized cohort. J Thorac Oncol 15: 426–435

    Google Scholar 

  • Rudin CM, Poirier JT, Byers LA, Dive C, Dowlati A, George J, Heymach JV, Johnson JE, Lehman JM, MacPherson D et al (2019) Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data. Nat Rev Cancer 19: 289–297

    Google Scholar 

  • Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez‐Abreu D, Wollner M, Yang JCH et al (2020) Pembrolizumab or placebo plus etoposide and platinum as first‐line therapy for extensive‐stage small‐cell lung cancer: randomized, double‐blind, phase III KEYNOTE‐604 study. J Clin Oncol 38: 2369–2379

    Google Scholar 

  • Ryu JS, Lim JH, Lee JM, Kim WC, Lee KH, Memon A, Lee SK, Yi BR, Kim HJ, Hwang SS (2016) Minimal pleural effusion in small cell lung cancer: Proportion, mechanisms, and prognostic effect. Radiology 278: 593–600

    Google Scholar 

  • Sabari JK, Lok BH, Laird JH, Poirier JT, Rudin CM (2017) Unravelling the biology of SCLC: implications for therapy. Nat Rev Clin Oncol 14: 549–561

    Google Scholar 

  • Sachs N, Papaspyropoulos A, Zomer‐van Ommen DD, Heo I, Böttinger L, Klay D, Weeber F, Huelsz‐Prince G, Iakobachvili N, Amatngalim GD et al (2019) Long‐term expanding human airway organoids for disease modeling. EMBO J 38: e100300

    Google Scholar 

  • Sakamoto S, Inoue H, Ohba S, Kohda Y, Usami I, Masuda T, Kawada M, Nomoto A (2015) New metastatic model of human small‐cell lung cancer by orthotopic transplantation in mice. Cancer Sci 106: 367–374

    Google Scholar 

  • Sato S, Hanibuchi M, Kuramoto T, Yamamori N, Goto H, Ogawa H, Mitsuhashi A, Van TT, Kakiuchi S, Akiyama SI et al (2013) Macrophage stimulating protein promotes liver metastases of small cell lung cancer cells by affecting the organ microenvironment. Clin Exp Metastasis 30: 333–344

    Google Scholar 

  • Saunders LR, Bankovich AJ, Anderson WC, Aujay MA, Bheddah S, Black KA, Desai R, Escarpe PA, Hampl J, Laysang A et al (2015) A DLL3‐targeted antibody‐drug conjugate eradicates high‐grade pulmonary neuroendocrine tumor‐initiating cells in vivo. Sci Transl Med 7: 302ra136

  • Schaffer BE, Park KS, Yiu G, Conklin JF, Lin C, Burkhart DL, Karnezis AN, Sweet‐Cordero EA, Sage J (2010) Loss of p130 accelerates tumor development in a mouse model for human small‐cell lung carcinoma. Cancer Res 70: 3877–3883

    Google Scholar 

  • Semenova EA, Kwon M, Monkhorst K, Song J‐Y, Bhaskaran R, Krijgsman O, Kuilman T, Peters D, Buikhuisen WA, Smit EF et al (2016) Transcription factor NFIB is a driver of small cell lung cancer progression in mice and marks metastatic disease in patients. Cell Rep 16: 631–643

    Google Scholar 

  • Sharma SK, Pourat J, Abdel‐Atti D, Carlin SD, Piersigilli A, Bankovich AJ, Gardner EE, Hamdy O, Isse K, Bheddah S et al (2017) Noninvasive interrogation of DLL3 expression in metastatic small cell lung cancer. Cancer Res 77: 3931–3941

    Google Scholar 

  • Shue YT, Lim JS, Sage J (2018) Tumor heterogeneity in small cell lung cancer defined and investigated in pre‐clinical mouse models. Transl Lung Cancer Res 7: 21–31

    Google Scholar 

  • Simpson KL, Stoney R, Frese KK, Simms N, Rowe W, Pearce SP, Humphrey S, Booth L, Morgan D, Dynowski M et al (2020) A biobank of small cell lung cancer CDX models elucidates inter‐ and intratumoral phenotypic heterogeneity. Nat. Cancer 1: 437–451

    Google Scholar 

  • Slotman B, Faivre‐Finn C, Kramer G, Rankin E, Snee M, Hatton M, Postmus P, Collette L, Musat E, Senan S (2007) Prophylactic cranial irradiation in extensive small‐cell lung cancer. N Engl J Med 357: 664–672

    Google Scholar 

  • Sodeur S, Ullrich S, Gustke H, Zangemeister‐Wittke U, Schumacher U (2009) Increased numbers of spontaneous SCLC metastasis in absence of NK cells after subcutaneous inoculation of different SCLC cell lines into pfp/rag2 double knock out mice. Cancer Lett 282: 146–151

    Google Scholar 

  • Sos ML, Dietlein F, Peifer M, Schoẗtle J, Balke‐Want H, Muller C, Koker M, Richters A, Heynck S, Malchers F et al (2012) A framework for identification of actionable cancer genome dependencies in small cell lung cancer. Proc Natl Acad Sci USA 109: 17034–17039

    Google Scholar 

  • Steele‐Perkins G, Plachez C, Butz KG, Yang G, Bachurski CJ, Kinsman SL, Litwack ED, Richards LJ, Gronostajski RM (2005) The transcription factor gene nfib is essential for both lung maturation and brain development. Mol Cell Biol 25: 685–698

    Google Scholar 

  • Stewart CA, Tong P, Cardnell RJ, Sen T, Li L, Gay CM, Masrorpour F, Fan Y, Bara RO, Feng Y et al (2017) Dynamic variations in epithelial‐to‐mesenchymal transition (EMT), ATM, and SLFN11 govern response to PARP inhibitors and cisplatin in small cell lung cancer. Oncotarget 8: 28575–28587

    Google Scholar 

  • Stewart CA, Gay CM, Xi Y, Sivajothi S, Sivakamasundari V, Fujimoto J, Bolisetty M, Hartsfield PM, Balasubramaniyan V, Chalishazar MD et al (2020) Single‐cell analyses reveal increased intratumoral heterogeneity after the onset of therapy resistance in small‐cell lung cancer. Nat Cancer 1: 423–436

    Google Scholar 

  • Stracke ML, Liotta LA (1992) Multi‐step cascade of tumor cell metastasis. In Vivo 6: 309–316

    Google Scholar 

  • Takahashi T, Nau MM, Chiba I, Birrer MJ, Rosenberg RK, Vinocour M, Levitt M, Pass H, Gazdar AF, Minna JD (1989) p53: A frequent target for genetic abnormalities in lung cancer. Science (80‐) 246: 491–494

    Google Scholar 

  • Takahashi T, Yamanaka T, Seto T, Harada H, Nokihara H, Saka H, Nishio M, Kaneda H, Takayama K, Ishimoto O et al (2017) Prophylactic cranial irradiation versus observation in patients with extensive‐disease small‐cell lung cancer: a multicentre, randomised, open‐label, phase 3 trial. Lancet Oncol 18: 663–671

    Google Scholar 

  • Taromi S, Kayser G, Catusse J, von Elverfeldt D, Reichardt W, Braun F, Weber WA, Zeiser R, Burger M (2016) CXCR4 antagonists suppress small cell lung cancer progression. Oncotarget 7: 85185–85195

    Google Scholar 

  • Tay RY, Fernández‐Gutiérrez F, Foy V, Burns K, Pierce J, Morris K, Priest L, Tugwood J, Ashcroft L, Lindsay CR et al (2019) Prognostic value of circulating tumour cells in limited‐stage small‐cell lung cancer: analysis of the concurrent once‐daily versus twice‐daily radiotherapy (CONVERT) randomised controlled trial. Ann Oncol 30: 1114–1120

    Google Scholar 

  • Wagenblast E, Soto M, Gutiérrez‐Ángel S, Hartl CA, Gable AL, Maceli AR, Erard N, Williams AM, Kim SY, Dickopf S et al (2015) A model of breast cancer heterogeneity reveals vascular mimicry as a driver of metastasis. Nature 520: 358–362

    Google Scholar 

  • Wang ZX, Lu BB, Yang JS, Wang KM, De W (2011) Adenovirus‐mediated SiRNA targeting c‐met inhibits proliferation and invasion of small‐cell lung cancer (SCLC) cells. J Surg Res 171: 127–135

    Google Scholar 

  • Wang X, Wang Z, Pan J, Lu ZY, Xu D, Zhang HJ, Wang SH, Huang DY, Chen XF (2020a) Patterns of extrathoracic metastases in different histological types of lung cancer. Front Oncol 10: 715

    Google Scholar 

  • Wang Y, Zheng Q, Jia B, An T, Zhao J, Wu M, Zhuo M, Li J, Zhong J, Chen H et al (2020b) Effects of surgery on survival of early‐stage patients with SCLC: propensity score analysis and nomogram construction in SEER database. Front Oncol 10: 626

    Google Scholar 

  • Weiskopf K, Jahchan NS, Schnorr PJ, Cristea S, Ring AM, Maute RL, Volkmer AK, Volkmer JP, Liu J, Lim JS et al (2016) CD47‐blocking immunotherapies stimulate macrophage‐mediated destruction of small‐cell lung cancer. J Clin Invest 126: 2610–2620

    Google Scholar 

  • Weksler B, Nason KS, Shende M, Landreneau RJ, Pennathur A (2012) Surgical resection should be considered for stage i and II small cell carcinoma of the lung. Ann Thorac Surg 94: 889–893

    Google Scholar 

  • Williamson SC, Metcalf RL, Trapani F, Mohan S, Antonello J, Abbott B, Leong HS, Chester CPE, Simms N, Polanski R et al (2016) Vasculogenic mimicry in small cell lung cancer. Nat Commun 7: 1–14

    Google Scholar 

  • Wu N, Jia D, Ibrahim AH, Bachurski CJ, Gronostajski RM, Macpherson D (2016) NFIB overexpression cooperates with Rb/p53 deletion to promote small cell lung cancer. Oncotarget 7: 57514–57524

    Google Scholar 

  • Yang D, Denny SK, Greenside PG, Chaikovsky AC, Brady JJ, Ouadah Y, Granja JM, Jahchan NS, Lim JS, Kwok S et al (2018) Intertumoral heterogeneity in SCLC is influenced by the cell type of origin. Cancer Discov 8: 1316–1331

    Google Scholar 

  • Yang D, Qu F, Cai H, Chuang CH, Lim JS, Jahchan N, Grüner BM, Kuo CS, Kong C, Oudin MJ et al (2019) Axon‐like protrusions promote small cell lung cancer migration and metastasis. Elife 8

  • Yin X, Yan D, Qiu M, Huang L, Yan S‐X (2019). Prophylactic cranial irradiation in small cell lung cancer: a systematic review and meta‐analysis. BMC Cancer 19: 95

    Google Scholar 

  • Zhao G, Gong L, Su D, Jin Y, Guo C, Yue M, Yao S, Qin Z, Ye Y, Tang Y et al (2019) Cullin5 deficiency promotes small‐cell lung cancer metastasis by stabilizing integrin β1. J Clin Invest 129: 972–987

    Google Scholar