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Animal Models for Small Cell Lung Cancer Research: Current Status and Future Perspectives

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Handbook of Animal Models and its Uses in Cancer Research
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Abstract

Small-cell lung cancer (SCLC), an aggressive neuroendocrine tumor characterized by enhanced proliferation rate and rapid early metastasis with low recovery rate, accounts for 15% of total lung cancer cases. Major risk factor for SCLC is tobacco smoking. Most of the patients were diagnosed at metastatic stage, and only one third in early stage of disease are amenable for curative multimodal therapy because of absence of precise symptoms and enhanced proliferation rate with metastatic nature. SCLC genomic analysis indicates prevalent rearrangements in chromosome with extensive mutation. Genomic analysis of SCLC revealed extensive chromosomal rearrangements and enhanced mutation rate leading to substantial intratumoral heterogeneity which limits the efficiency of therapy and relapse of tumor due to development of therapeutic resistance. Unraveling the mechanism of pathogenesis such as initiation, progression, and metastasis of SCLC is essential to identify the novel vulnerabilities amenable for targeted therapeutic approaches. Construction of several animal models such as chemical induction models, patient-derived xenotransplantation, gene programming harboring mutations associated with SCLC not only facilitated to unravel the biological pathways responsible for incidence and prognosis of SCLC, but also to explore the anticancer drugs and gene therapy. This chapter focuses on several animal models depicting the characteristic features of SCLC, combined with latest progress and future research of animal model used for SCLC.

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References

  • Anderson WC, Boyd MB, Aguilar J, Pickell B, Laysang A, Pysz MA et al (2015) Initiation and characterization of small cell lung cancer patient derived xenografts from ultrasound-guided transbronchial needle aspirates. PLoS One 10(5):e0125255. https://doi.org/10.1371/journal.pone.0125255

  • Austin JH et al (2012) Small-cell carcinoma of the lung detected by CT screening: stage distribution and curability. Lung Cancer 76:339–343

    Article  Google Scholar 

  • Barnes D, van der Bosch J, Masui H, Miyazaki K, Sato G (1981) The culture of human tumor cells in serum-free medium. Methods Enzymol 79(pt 8):368–339

    Article  CAS  Google Scholar 

  • Barta JA, Powell CA, Wisnivesky JP (2019) Global epidemiology of lung cancer. Ann Glob Health 85(1):8. https://doi.org/10.5334/aogh.2419

    Article  Google Scholar 

  • Brown HK, Schiavone K, Tazzyman S, Heymann D, Chico TJ (2017) Zebrafish xenograft models of cancer and metastasis for drug discovery. Expert Opin Drug Discovery 12(4):379–389

    Article  CAS  Google Scholar 

  • Carney DN, Gazdar AF, Bepler G et al (1985) Establishment and identification of small cell lung cancer cell lines having classic and variant features. Cancer Res5 45(6):2913–2923

    CAS  Google Scholar 

  • Carter B, Glisson B, Truong M, Erasmus J (2014) Small cell lung carcinoma: staging, imaging, and treatment considerations. Radiographics 34:1707–1721. https://doi.org/10.1148/rg.346140178

    Article  Google Scholar 

  • Celià-Terrassa T, Kang Y (2016) Distinctive properties of metastasis-initiating cells. Genes Dev 30:892–908. https://doi.org/10.1101/gad.277681.116

    Article  CAS  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

    Article  CAS  Google Scholar 

  • Daniel VC, Marchionni L, Hierman JS, Rhodes JT, Devereux WL, Rudin CM et al (2009) A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitro. Cancer Res 69:3364–3373. https://doi.org/10.1158/0008-5472.CAN-08-4210. PMID: 19351829

    Article  CAS  Google Scholar 

  • Denninghoff V, Russo A, de Miguel-Pérez D et al (2021) Small cell lung cancer: state of the art of the molecular and genetic landscape and novel perspective. Cancers 13:1723. https://doi.org/10.3390/cancers13071723

  • Dutt A, Wong KK (2006) Mouse models of lung cancer. Clinical Cancer Research. 12(14 Pt 2), 4396s–4402s. https://doi.org/10.1158/1078-0432.CCR-06-0414

  • Franco F, Carcereny E, Guirado M, Ortega AL, López-Castro R, Rodríguez-Abreu D et al (2021) Epidemiology, treatment, and survival in small cell lung cancer in Spain: data from the thoracic tumor registry. PLoS One 16(6):e0251761. https://doi.org/10.1371/journal.pone.0251761

    Article  CAS  Google Scholar 

  • Fruh M et al (2013) Small-cell lung cancer (SCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 24:vi99–vi105

    Article  Google Scholar 

  • Gazdar AF, Hirsch FR, Minna JD (2016 Mar) From mice to men and back: an assessment of preclinical model systems for the study of lung cancers. J Thorac Oncol 11(3):287–299. https://doi.org/10.1016/j.jtho.2015.10.009

  • George J, Lim JS, Jang SJ, Cun Y, Ozretic L, Kong G, Leenders F, Lu X, Fernández-Cuesta L, Bosco G et al (2015) Comprehensive genomic profiles of small cell lung cancer. Nature. https://doi.org/10.1038/nature14664

  • Hodgkinson CL, Morrow CJ, Li Y, Metcalf RL, Rothwell DG, Trapani F et al (2014) Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Nat Med 8:897–903.10. https://doi.org/10.1038/nm.3600. PMID: 24880617

    Article  CAS  Google Scholar 

  • Hsu PD, Lander ES, Zhang F (2014) Development and applications of CRISPR–Cas9 for genome engineering. Cell 157:1262–1278

    Article  CAS  Google Scholar 

  • Huang HW, Bow YD, Wang CY, Chen YC, Fu PR, Chang KF, Wang TW, Tseng CH, Chen YL, Chiu CC (2020) DFIQ, a novel quinoline derivative, shows anticancer potential by inducing apoptosis and autophagy in NSCLC cell and in vivo zebrafish xenograft models. Cancers 12(5):1348. https://doi.org/10.3390/cancers12051348

    Article  CAS  Google Scholar 

  • Huijbers IJ, Krimpenfort P, Berns A, Jonkers J (2011) Rapid validation of cancer genes in chimeras derived from established genetically engineered mouse models. BioEssays 33:701e710

    Article  Google Scholar 

  • Huijbers IJ, Bin Ali R, Pritchard C et al (2014) Rapid target gene validation in complex cancer mouse models using re-derived embryonic stem cells. EMBO Mol Med 6:212–225

    Article  CAS  Google Scholar 

  • Inamura K (2017) Lung cancer: understanding its molecular pathology and the 2015 WHO classification. Front Oncol 7:193. https://doi.org/10.3389/fonc.2017.00193

    Article  Google Scholar 

  • Indini A, Rijavec E, Bareggi C, Grossi F (2020) Novel treatment strategies for early-stage lung cancer: the oncologist’s perspective. J Thorac Dis 12(6):3390–3398. https://doi.org/10.21037/jtd.2020.02.46

    Article  Google Scholar 

  • Jiang Y, Wells A, Sylakowski K, Clark AM, Ma B (2019) Adult stem cell functioning in the tumor micro-environment. Int J Mol Sci 20(10):2566

    Article  CAS  Google Scholar 

  • Jin W, Lei Z, Xu S et al (2021) Genetic mutation analysis in small cell lung cancer by a novel NGS-based targeted resequencing gene panel and relation with clinical features. Biomed Res Int. Article ID 3609028 8. https://doi.org/10.1155/2021/3609028

  • Kalemkerian GP, Akerley W, Bogner P, National Comprehensive Cancer Network et al (2013) Small cell lung cancer. J Natl Compr Cancer Netw 11(1):78–98. https://doi.org/10.6004/jnccn.2013.0011

    Article  CAS  Google Scholar 

  • Kanaji N et al (2014) Paraneoplastic syndromes associated with lung cancer. World J Clin Oncol 5:197–223

    Article  Google Scholar 

  • Kim DW, Kim KC, Kim KB, Dunn CT, Park KS (2018) Transcriptional deregulation underlying the pathogenesis of small cell lung cancer. Trans Lung Cancer Res 7(1):4–20. https://doi.org/10.21037/tlcr.2017.10.07

    Article  CAS  Google Scholar 

  • Klameth L, Rath B, Hochmaier M et al (2017) Small cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance. Sci Rep 7(1):5337. Published 2017 Jul 13. https://doi.org/10.1038/s41598-017-05562-

    Article  Google Scholar 

  • Kwon M-c, Berns A (2013) Mouse models for lung cancer. Mol Oncol 7:165–177

    Article  CAS  Google Scholar 

  • Lamichhane DK, Kim HC, Choi CM, Shin MH, Shim YM, Leem JH, Ryu JS, Nam HS, Park SM (2017) Lung cancer risk and residential exposure to air pollution: a Korean population-based case-control study. Yonsei Med J 58(6):1111–1118. https://doi.org/10.3349/ymj.2017.58.6.1111

    Article  CAS  Google Scholar 

  • Latimer KM, Mott TF (2015) Lung cancer: diagnosis, treatment principles, and screening. Am Fam Physician 91(4):250–256. PMID: 25955626

    Google Scholar 

  • Leong TL, Marini KD, Rossello FJ, Jayasekara SN, Russell PA, Prodanovic Z et al (2014) Genomic characterisation of small cell lung cancer patient-derived xenografts generated from endobronchial ultrasound-guided transbronchial needle aspiration specimens. PLoS One 9(9):e106862. https://doi.org/10.1371/journal.pone.0106862. PMID: 25191746

    Article  CAS  Google Scholar 

  • MacRae CA, Peterson RT (2015) Zebrafish as tools for drug discovery. Nat Rev Drug Discov 14(10):721–731

    Article  CAS  Google Scholar 

  • Malhotra J, Malvezzi M, Negri E, La Vecchia C, Boffetta P (2016) Risk factors for lung cancer worldwide. Eur Respir J 48(3):889–902. https://doi.org/10.1183/13993003.00359-2016. Epub 2016 May 12. PMID: 27174888

    Article  Google Scholar 

  • Malyla V, Paudel KR, Shukla SD, Donovan C, Wadhwa R, Pickles S, Chimankar V, Sahu P, Bielefeldt-Ohmann H, Bebawy M, Hansbro PM, Dua K (2020) Recent advances in experimental animal models of lung cancer. Future Med Chem 12(7):567–570. https://doi.org/10.4155/fmc-2019-0338

    Article  CAS  Google Scholar 

  • Moro M, Bertolini G, Tortoreto M, Pastorino U, Sozzi G, Roz L (2012) Patient-derived xenografts of non small cell lung cancer: resurgence of an old model for investigation of modern concepts of tailored therapy and cancer stem cells. BioMed Res Inte 2012:11. Article ID 568567. https://doi.org/10.1155/2012/568567

  • 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

    Article  CAS  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

    Article  CAS  Google Scholar 

  • Oboshi S, Tsugawa S, Seido T, Shimosato Y, Koide T (1971) A new floating cell line derived from human pulmonary carcinoma of oat cell type. Gann 62(6):505–514

    CAS  Google Scholar 

  • Oie HK, Russell EK, Carney DN, Gazdar AF (1996) Cell culture methods for the establishment of the NCI series of lung cancer cell lines. J Cell Biochem 24:24–31

    Article  CAS  Google Scholar 

  • PaoW MVA, Kris MG (2004) ‘Targeting’ the epidermal growthf actor receptor tyrosine kinase withg efitinib (Iressa) in non-small cell lung cancer (NSCLC). Semin Cancer Biol 14:33–40

    Article  Google Scholar 

  • Park K-S, Martelotto LG, Peifer M, Sos ML, Karnezis AN, Mahjoub MR, Bernard K, Conklin JF, Szczepny A, Yuan J et al (2011) A crucial requirement for hedgehog signaling in small cell lung cancer. Nat Med 17:150–1508

    Google Scholar 

  • Pettengill OS, Faulkner CS, Wurster-Hill DH et al (1977) Isolation and characterization of a hormone-producing cell line from human small cell anaplastic carcinoma of the lung. J Natl Cancer Inst 58(3):511–518

    Article  CAS  Google Scholar 

  • Raso MG, Bota-Rabassedas N, Wistuba II (2021) Pathology and classification of SCLC. Cancers 13:820. https://doi.org/10.3390/cancers13040820

  • Rodríguez-Martínez Á, Torres-Durán M, Barros-Dios JM, Ruano-Ravina A (2018) Residential radon and small cell lung cancer. A systematic review Cancer Lett 10(426):57–62. https://doi.org/10.1016/j.canlet.2018.04.003

    Article  CAS  Google Scholar 

  • Roschke AV, Tonon G, Gehlhaus KS, McTyre N, Bussey KJ, Lababidi S et al (2003) Karyotypic complexity of the NCI-60 drug-screening panel. Cancer Res 63:8634–8647. PMID: 14695175

    CAS  Google Scholar 

  • Rudin CM, Brambilla E, Faivre-Finn C et al (2021) Small-cell lung cancer. Nat Rev Dis Primers 7:3. https://doi.org/10.1038/s41572-020-00235-0

    Article  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Shen W, Pu J, Sun J et al (2020) Zebrafish xenograft model of human lung cancer for studying the function of LINC00152 in cell proliferation and invasion. Cancer Cell Int 20:376. https://doi.org/10.1186/s12935-020-01460-z

    Article  CAS  Google Scholar 

  • Singh M, Murriel CL, Johnson L (2012) Genetically engineered mouse models: closing the gap between preclinical data and trial outcomes. Cancer Res 72:2695–2700

    Google Scholar 

  • Song H, Yao E, Lin C, Gacayan R, Chen M-H, Chuang P-T (2012) Functional characterization of pulmonary neuroendocrine cells in lung development, injury, and tumorigenesis. Proc Natl Acad Sci 109:17531–17536

    Article  CAS  Google Scholar 

  • Sriuranpong V, Borges MW, Ravi RK et al (2001) Notch signaling induces cell cycle arrest in small cell lung cancer cells. Cancer Res 61(7):3200–3205

    CAS  Google Scholar 

  • Sutherland KD, Proost N, Brouns I, Adriaensen D, Song J-Y, Berns A (2011) Cell of origin of small cell lung cancer: inactivation of Trp53 and Rb1 in distinct cell types of adult mouse lung. Cancer Cell 19:754–764

    Article  CAS  Google Scholar 

  • Tang Q, Moore JC, Ignatius MS et al (2016) Imaging tumour cell heterogeneity following cell transplantation into optically clear immune-deficient zebrafish. Nat Commun 7:10358. https://doi.org/10.1038/ncomms10358

    Article  CAS  Google Scholar 

  • Tentler JJ, Tan AC, Weekes CD, Jimeno A, Leong S, Pitts TM et al (2012) Patient-derived tumour xenografts as models for oncology drug development. Nat Rev Clin Oncol 9:338–350. https://doi.org/10.1038/nrclinonc.2012.61. PMID: 22508028

    Article  CAS  Google Scholar 

  • Tlemsani C, Pongor L, Elloumi F et al (2020) SCLC-CellMiner: a resource for small cell lung cancer cell line genomics and pharmacology based on genomic signatures. Cell Rep 33(3):108296. https://doi.org/10.1016/j.celrep.2020.108296

    Article  CAS  Google Scholar 

  • Travis WD (2014) Pathology and diagnosis of neuroendocrine tumors: lung neuroendocrine. Thorac Surg Clin 24:257–266

    Article  Google Scholar 

  • Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG (2015a) WHO classification of tumours of the lung, pleura, thymus and heart, 4th edn. IARC, Lyon

    Google Scholar 

  • Travis WD et al (2015b) The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol 10:1243–1260

    Google Scholar 

  • van Meerbeeck JP, Fennell DA, De Ruysscher DK (2011) Small-cell lung cancer. Lancet 378:1741–1755

    Google Scholar 

  • Wang J et al (2017) Genetic predisposition to lung cancer: comprehensive literature integration, meta-analysis, and multiple evidence assessment of candidate-gene association studies. Sci Rep 7:8371. https://doi.org/10.1038/s41598-017-07737-0

    Article  CAS  Google Scholar 

  • Wang S, Zimmermann S, Parikh K, Mansfield AD, Adjei AA (2019) Current diagnosis and management of small-cell lung cancer. Thematic review on neoplastic hematology and medical oncology. Mayo Clin Proc 94(8):1599–1622

    Google Scholar 

  • Welsh CE, Miller DR, Manly KF, Wang J, McMillan L, Morahan G, Mott R, Iraqi FA, Threadgill DW, de Villena FPM (2012) Status and access to the collaborative cross population. Mamm Genome 23:706–712.

    Google Scholar 

  • West H (2019) Moving beyond limited and extensive staging of small cell lung cancer. JAMA Oncol 5(3):e185187. https://doi.org/10.1001/jamaoncol.2018.5187

    Article  Google Scholar 

  • Wild CP (2019) The global cancer burden: necessity is the mother of prevention. Nat Rev Cancer 19(3):123–124. https://doi.org/10.1038/s41568-019-0110-3

    Article  CAS  Google Scholar 

  • Williams SA, Anderson WC, Santaguida MT, Dylla SD (2013) Patient-derived xenografts, the cancer stem cell paradigm, and cancer pathobiology in the 21st century. Lab Invest 93:970–982. https://doi.org/10.1038/labinvest.2013.92

    Article  Google Scholar 

  • Xia Y, Yeddula N, Leblanc M et al (2012) Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model. Nat Cell Biol 14:257–265. https://doi.org/10.1038/ncb2428

  • Li X-Y, Huang L-T, Wu J-Q, He M-F, Zhu S-H, Zhan P, Lv T-F, Song Y (2019) Zebrafish xenograft model of human lung cancer for evaluating Osimertinib resistance. Biomed Res Int 3129748, 10. https://doi.org/10.1155/2019/3129748

  • Yang S, Zhang Z, Wang Q (2019) Emerging therapies for small cell lung cancer. J Hematol Oncol 12:47. https://doi.org/10.1186/s13045-019-0736-3

    Article  Google Scholar 

  • Yu N, Zhou J, Cui F, Tang X (2015) Circulating tumor cells in lung cancer: detection methods and clinical applications. Lung 193:157–171. https://doi.org/10.1007/s00408-015-9697-7

    Article  CAS  Google Scholar 

  • Zhao G, Zhao Z, Jia Y (2019) Advances in preclinical models of small cell lung cancer. Med One 2019(4):e190019. https://doi.org/10.20900/mo.20190019

    Article  Google Scholar 

  • Zheng M (2016) Classification and pathology of lung cancer. Surg Oncol Clin N Am 25(3):447–468. https://doi.org/10.1016/j.soc.2016.02.003. PMID: 27261908

    Article  Google Scholar 

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Acknowledgments

Dr. N. Suganthy thanks the RUSA-Phase 2.0 grant (No. F. 24-51/2014-U, Policy (TN Multi-Gen), Dept. of Edn. Govt.of India, (Dated: 09.10.2018) for the financial support in general

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Correspondence to Suganthy Natarajan .

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Natarajan, S. (2023). Animal Models for Small Cell Lung Cancer Research: Current Status and Future Perspectives. In: Pathak, S., Banerjee, A., Bisgin, A. (eds) Handbook of Animal Models and its Uses in Cancer Research. Springer, Singapore. https://doi.org/10.1007/978-981-19-3824-5_60

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