{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:18:21Z","timestamp":1790774301272,"version":"4.1.0"},"reference-count":230,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T00:00:00Z","timestamp":1558051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Lung cancer is the leading cause of cancer-related deaths worldwide. With a focus on histology, there are two major subtypes: Non-small cell lung cancer (NSCLC) (the more frequent subtype), and small cell lung cancer (SCLC) (the more aggressive one). Even though SCLC, in general, is a chemosensitive malignancy, relapses following induction therapy are frequent. The standard of care treatment of SCLC consists of platinum-based chemotherapy in combination with etoposide that is subsequently enhanced by PD-L1-inhibiting atezolizumab in the extensive-stage disease, as the addition of immune-checkpoint inhibition yielded improved overall survival. Although there are promising molecular pathways with potential therapeutic impacts, targeted therapies are still not an integral part of routine treatment. Against this background, we evaluated current literature for potential new molecular candidates such as surface markers (e.g., DLL3, TROP-2 or CD56), apoptotic factors (e.g., BCL-2, BET), genetic alterations (e.g., CREBBP, NOTCH or PTEN) or vascular markers (e.g., VEGF, FGFR1 or CD13). Apart from these factors, the application of so-called \u2018poly-(ADP)-ribose polymerases\u2019 (PARP) inhibitors can influence tumor repair mechanisms and thus offer new perspectives for future treatment. Another promising therapeutic concept is the inhibition of \u2018enhancer of zeste homolog 2\u2019 (EZH2) in the loss of function of tumor suppressors or amplification of (proto-) oncogenes. Considering the poor prognosis of SCLC patients, new molecular pathways require further investigation to augment our therapeutic armamentarium in the future.<\/jats:p>","DOI":"10.3390\/cancers11050690","type":"journal-article","created":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T11:06:46Z","timestamp":1558091206000},"page":"690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Future Options of Molecular-Targeted Therapy in Small Cell Lung Cancer"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1644-3573","authenticated-orcid":false,"given":"Arik Bernard","family":"Schulze","sequence":"first","affiliation":[{"name":"Department of Medicine A, Hematology, Oncology and Pulmonary Medicine, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Evers","sequence":"additional","affiliation":[{"name":"Department of Medicine A, Hematology, Oncology and Pulmonary Medicine, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Kerkhoff","sequence":"additional","affiliation":[{"name":"Department of Medicine A, Hematology, Oncology and Pulmonary Medicine, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mohr","sequence":"additional","affiliation":[{"name":"Department of Medicine A, Hematology, Oncology and Pulmonary Medicine, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schliemann","sequence":"additional","affiliation":[{"name":"Department of Medicine A, Hematology, Oncology and Pulmonary Medicine, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang E.","family":"Berdel","sequence":"additional","affiliation":[{"name":"Department of Medicine A, Hematology, Oncology and Pulmonary Medicine, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars Henning","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Medicine A, Hematology, Oncology and Pulmonary Medicine, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012","volume":"136","author":"Ferlay","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_2","unstructured":"Travis, W.D., Brambilla, E., M\u00fcller-Hermelink, H.K., and Harris, C. (2004). World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart, IARC Press."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"National Lung Screening Trial Research Team, Aberle, D.R., Adams, A.M., Berg, C.D., Black, W.C., Clapp, J.D., Fagerstrom, R.M., Gareen, I.F., Gatsonis, C., and Marcus, P.M. (2011). Reduced lung-cancer mortality with low-dose computed tomographic screening. N. Engl. J. Med., 365, 395\u2013409.","DOI":"10.1056\/NEJMoa1102873"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1056\/NEJMoa1808779","article-title":"A randomized trial of e-cigarettes versus nicotine-replacement therapy","volume":"380","author":"Hajek","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1056\/NEJMoa1715907","article-title":"Higher lung cancer incidence in young women than young men in the United States","volume":"378","author":"Jemal","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1097\/JTO.0000000000000630","article-title":"The 2015 World health organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification","volume":"10","author":"Travis","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1038\/modpathol.2011.150","article-title":"Update on small cell carcinoma and its differentiation from squamous cell carcinoma and other non-small cell carcinomas","volume":"25","author":"Travis","year":"2012","journal-title":"Mod. Pathol."},{"key":"ref_8","first-page":"296","article-title":"Der Lungenkrebs, die Bergkrankheit in den Schneeberger Gruben","volume":"30","author":"Hesse","year":"1879","journal-title":"Vjschr Gerichtl Med Offen Sanit."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/path.1700290304","article-title":"The nature of the \u2018oat-celled sarcoma\u2019 of the mediastinum","volume":"29","author":"Barnard","year":"1926","journal-title":"J. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/his.13394","article-title":"Molecular alterations of neuroendocrine tumours of the lung","volume":"72","author":"Rossi","year":"2018","journal-title":"Histopathology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"108936","DOI":"10.18632\/oncotarget.22426","article-title":"Therapeutic strategies and genetic profile comparisons in small cell carcinoma and large cell neuroendocrine carcinoma of the lung using next-generation sequencing","volume":"8","author":"Ito","year":"2017","journal-title":"Oncotarget"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nature14664","article-title":"Comprehensive genomic profiles of small cell lung cancer","volume":"524","author":"George","year":"2015","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S1535-6108(03)00220-4","article-title":"Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model","volume":"4","author":"Meuwissen","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.ccr.2011.04.019","article-title":"Cell of origin of small cell lung cancer: Inactivation of Trp53 and Rb1 in distinct cell types of adult mouse lung","volume":"19","author":"Sutherland","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.ccr.2010.12.021","article-title":"A functional role for tumor cell heterogeneity in a mouse model of small cell lung cancer","volume":"19","author":"Calbo","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.ccell.2016.12.005","article-title":"MYC drives progression of small cell lung cancer to a variant neuroendocrine subtype with vulnerability to aurora kinase inhibition","volume":"31","author":"Mollaoglu","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.bbrc.2016.12.117","article-title":"The notch ligand delta-like 3 promotes tumor growth and inhibits notch signaling in lung cancer cells in mice","volume":"483","author":"Deng","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.lungcan.2017.11.018","article-title":"Prevalence of Delta-like protein 3 expression in patients with small cell lung cancer","volume":"115","author":"Tanaka","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1200\/JCO.18.01585","article-title":"EGFR -Mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: Clinical outcomes","volume":"37","author":"Marcoux","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/ncomms7377","article-title":"RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer","volume":"6","author":"Niederst","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.cancergen.2017.05.003","article-title":"Significantly mutated genes and regulatory pathways in SCLC\u2014A meta-analysis","volume":"216\u2013217","author":"Sundaresan","year":"2017","journal-title":"Cancer Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.lungcan.2014.10.002","article-title":"Gene mutations in small-cell lung cancer (SCLC): Results of a panel of 6 genes in a cohort of Italian patients","volume":"86","author":"Bordi","year":"2014","journal-title":"Lung Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.2147\/OTT.S159612","article-title":"EGFR, KRAS, BRAF, PTEN, and PIK3CA mutation in plasma of small cell lung cancer patients","volume":"11","author":"Lu","year":"2018","journal-title":"Onco. Targets Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1093\/nar\/gky1015","article-title":"COSMIC: The catalogue of somatic mutations in cancer","volume":"47","author":"Tate","year":"2018","journal-title":"Nucl. Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1007\/s00432-015-1989-z","article-title":"Expression profiling of receptor tyrosine kinases in high-grade neuroendocrine carcinoma of the lung: A comparative analysis with adenocarcinoma and squamous cell carcinoma","volume":"141","author":"Matsumura","year":"2015","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"111","DOI":"10.2217\/pme-2017-0069","article-title":"ALK-rearranged adenocarcinoma transformed to small-cell lung cancer: A new entity with specific prognosis and treatment?","volume":"15","author":"Hobeika","year":"2018","journal-title":"Per. Med."},{"key":"ref_27","first-page":"261","article-title":"Successful sequential treatment of refractory tumors caused by small cell carcinoma transformation and EGFR-T790M mutation diagnosed by repeated genetic testing in a patient with lung adenocarcinoma harboring epidermal growth factor receptor mutations: A","volume":"25","author":"Nishioka","year":"2018","journal-title":"Respir. Med. Case Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/1759-7714.12927","article-title":"Overcoming T790M mutant small cell lung cancer with the third-generation EGFR-TKI osimertinib","volume":"10","author":"Tang","year":"2019","journal-title":"Thorac. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"160","DOI":"10.21037\/atm.2018.05.02","article-title":"Emerging application of genomics-guided therapeutics in personalized lung cancer treatment","volume":"6","author":"Zaman","year":"2018","journal-title":"Ann. Transl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.jtho.2016.12.011","article-title":"Small cell lung cancer exhibits frequent inactivating mutations in the histone methyltransferase KMT2D\/MLL2: CALGB 151111 (Alliance)","volume":"12","author":"Augert","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1002\/gcc.22076","article-title":"Genome-wide identification of genes with amplification and\/or fusion in small cell lung cancer","volume":"52","author":"Iwakawa","year":"2013","journal-title":"Genes Chromosom Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/modpathol.2013.141","article-title":"Fibroblast growth factor receptor 1 (FGFR1) amplification is a potential therapeutic target in small-cell lung cancer","volume":"27","author":"Schultheis","year":"2014","journal-title":"Mod. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1038\/ng.2405","article-title":"Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer","volume":"44","author":"Rudin","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3707","DOI":"10.21873\/anticanres.12649","article-title":"Prevalence of enhancer of zeste homolog 2 in patients with resected small cell lung cancer","volume":"38","author":"Toyokawa","year":"2018","journal-title":"Anticancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.steroids.2016.05.008","article-title":"Prognostic relevance of estrogen receptor \u03b1, \u03b2 and aromatase expression in non-small cell lung cancer","volume":"113","author":"Skjefstad","year":"2016","journal-title":"Steroids"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus chemotherapy for PD-L1\u2013positive non\u2013small-cell lung cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1056\/NEJMoa1507643","article-title":"Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer","volume":"373","author":"Borghaei","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1200\/JCO.2016.66.9929","article-title":"Nivolumab Monotherapy for first-line treatment of advanced non-small-cell lung cancer","volume":"34","author":"Gettinger","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1200\/JCO.2016.66.9861","article-title":"Nivolumab in combination with platinum-based doublet chemotherapy for first-line treatment of advanced non-small-cell lung cancer","volume":"34","author":"Rizvi","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1056\/NEJMoa1504627","article-title":"Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer","volume":"373","author":"Brahmer","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1016\/S1470-2045(16)30498-3","article-title":"Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study","volume":"17","author":"Langer","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0140-6736(16)32517-X","article-title":"Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): A phase 3, open-label, multicentre randomised controlled trial","volume":"389","author":"Rittmeyer","year":"2017","journal-title":"Lancet"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1056\/NEJMoa1809064","article-title":"First-Line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer","volume":"379","author":"Horn","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jtho.2018.10.003","article-title":"Third-line nivolumab monotherapy in recurrent SCLC: CheckMate 032","volume":"14","author":"Ready","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1093\/annonc\/mdy511.004","article-title":"Efficacy and safety of nivolumab (nivo) monotherapy versus chemotherapy (chemo) in recurrent small cell lung cancer (SCLC): Results from CheckMate 331","volume":"29","author":"Reck","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S1470-2045(16)30098-5","article-title":"Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): A multicentre, open-label, phase 1\/2 trial","volume":"17","author":"Antonia","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8506","DOI":"10.1200\/JCO.2018.36.15_suppl.8506","article-title":"Phase 2 study of pembrolizumab in advanced small-cell lung cancer (SCLC): KEYNOTE-158","volume":"36","author":"Chung","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.6004\/jnccn.2018.0079","article-title":"NCCN guidelines\u00ae insights: Small cell lung cancer, version 2.2018 featured updates to the NCCN guidelines","volume":"16","author":"Kalemkerian","year":"2018","journal-title":"JNCCN J. Natl. Compr. Cancer Netw."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1056\/NEJMoa1501824","article-title":"Pembrolizumab for the treatment of non-small-cell lung cancer","volume":"372","author":"Garon","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.ejca.2014.12.006","article-title":"PD-L1 expression in small cell neuroendocrine carcinomas","volume":"51","author":"Schultheis","year":"2015","journal-title":"Eur. J. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4689","DOI":"10.21037\/jtd.2018.07.120","article-title":"Tumor mutational burden (TMB) as a biomarker of response to immunotherapy in small cell lung cancer","volume":"10","author":"Boumber","year":"2018","journal-title":"J. Thorac. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.ccell.2018.04.001","article-title":"tumor mutational burden and efficacy of nivolumab monotherapy and in combination with ipilimumab in small-cell lung cancer","volume":"33","author":"Hellmann","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.ccell.2018.03.018","article-title":"Genomic features of response to combination immunotherapy in patients with advanced non-small-cell lung cancer","volume":"33","author":"Hellmann","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wang, S., Zhang, J., He, Z., Wu, K., and Liu, X. (2019). The predictive power of tumor mutational burden in lung cancer immunotherapy response is influenced by patients\u2019 sex. Int. J. Cancer.","DOI":"10.1002\/ijc.32327"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1093\/annonc\/mdy326","article-title":"Immunotherapeutic maintenance treatment with toll-like receptor 9 agonist lefitolimod in patients with extensive-stage small-cell lung cancer: Results from the exploratory, controlled, randomized, international phase II IMPULSE study","volume":"29","author":"Thomas","year":"2018","journal-title":"Ann. Oncol. Off. J. Eur. Soc. Med. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1172\/JCI81603","article-title":"CD47-blocking immunotherapies stimulate macrophage-mediated destruction of small-cell lung cancer","volume":"126","author":"Weiskopf","year":"2016","journal-title":"J. Clin. Invest."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.radonc.2018.12.014","article-title":"Prophylactic cranial irradiation in stage IV small cell lung cancer: Selection of patients amongst European IASLC and ESTRO experts","volume":"133","author":"Putora","year":"2019","journal-title":"Radiother. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.radonc.2018.11.005","article-title":"Optimal timing of thoracic radiotherapy in limited stage small cell lung cancer (SCLC) with daily fractionation: A brief report","volume":"132","author":"Hasan","year":"2019","journal-title":"Radiother. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.canlet.2019.02.048","article-title":"Mechanisms and therapeutic potentials of cancer immunotherapy in combination with radiotherapy and\/or chemotherapy","volume":"452","author":"Yu","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/annonc\/mdx716","article-title":"Randomized phase III trial of low-molecular-weight heparin enoxaparin in addition to standard treatment in small-cell lung cancer: The RASTEN trial","volume":"29","author":"Ek","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Gezelius, E., Kristensen, A.F., Bendahl, P.O., Hisada, Y., Kristensen, S.R., Ek, L., Bergman, B., Wallberg, M., Falkmer, U., and Mackman, N. (2018). Coagulation biomarkers and prediction of venous thromboembolism and survival in small cell lung cancer: A sub-study of RASTEN\u2014A randomized trial with low molecular weight heparin. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0207387"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Zab\u0142ocka-S\u0142owi\u0144ska, K., P\u0142aczkowska, S., Sk\u00f3rska, K., Prescha, A., Pawe\u0142czyk, K., Por\u0119bska, I., Kosacka, M., and Grajeta, H. (2019). Oxidative stress in lung cancer patients is associated with altered serum markers of lipid metabolism. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0215246"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1200\/JCO.2016.69.7391","article-title":"Multicenter, phase III, randomized, double-blind, placebo-controlled trial of pravastatin added to first-line standard chemotherapy in small-cell lung cancer (LUNGSTAR)","volume":"35","author":"Seckl","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1200\/JCO.1983.1.9.582","article-title":"Monoclonal antibodies in cancer therapy","volume":"1","author":"Oldham","year":"1983","journal-title":"J. Clin. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1517\/14712598.3.7.1133","article-title":"Antibodies as therapeutic agents: vive la renaissance!","volume":"3","author":"Stockwin","year":"2003","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1007\/s00280-015-2861-1","article-title":"Targeted therapy in cancer","volume":"76","author":"Tsimberidou","year":"2015","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s13277-015-3184-x","article-title":"Novel and emerging targeted-based cancer therapy agents and methods","volume":"36","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_69","first-page":"1005","article-title":"Small Molecule inhibitors: suitable drugs for targeted- based cancer therapy","volume":"1","year":"2018","journal-title":"Am. J. Leuk. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.chembiol.2014.09.001","article-title":"Small-molecule inhibitors of protein-protein interactions: Progressing toward the reality","volume":"21","author":"Arkin","year":"2014","journal-title":"Chem. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1200\/JCO.2016.69.4844","article-title":"Italian, multicenter, phase III, randomized study of cisplatin plus etoposide with or without bevacizumab as first-line treatment in extensive-disease small-cell lung cancer: The GOIRC-AIFA FARM6PMFJM trial","volume":"35","author":"Tiseo","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.lungcan.2016.04.002","article-title":"A phase II study of nintedanib in patients with relapsed small cell lung cancer","volume":"96","author":"Han","year":"2016","journal-title":"Lung Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1200\/JCO.2014.57.3105","article-title":"Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study - CALGB 30504 (Alliance)","volume":"33","author":"Ready","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/cncr.30287","article-title":"A randomized, double-blind, phase 2 trial of platinum therapy plus etoposide with or without concurrent vandetanib (ZD6474) in patients with previously untreated extensive-stage small cell lung cancer: Hoosier cancer research network LUN06-113","volume":"123","author":"Sanborn","year":"2017","journal-title":"Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ejca.2015.10.016","article-title":"Sunitinib (SU11248) in patients with chemo naive extensive small cell lung cancer or who have a \u2018chemosensitive\u2019 relapse: A single-arm phase II study (EORTC-08061)","volume":"54","author":"Abdelraouf","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1200\/JCO.2007.11.8109","article-title":"Phase III double-blind, placebo-controlled study of thalidomide in extensive-disease small-cell lung cancer after response to chemotherapy: An intergroup study FNCLCC cleo04-IFCT 00-01","volume":"25","author":"Pujol","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1093\/jnci\/djp200","article-title":"Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: A randomized, double-blind, placebo-controlled trial","volume":"101","author":"Lee","year":"2009","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1097\/JTO.0b013e318282707b","article-title":"A phase I study of pomalidomide (CC-4047) in combination with cisplatin and etoposide in patients with extensive-stage small-cell lung cancer","volume":"8","author":"Ellis","year":"2013","journal-title":"J. Thorac. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/annonc\/mdx386.004","article-title":"1530PDResults of a randomized, placebo-controlled, phase 2 study of tarextumab (TRXT, anti-Notch2\/3) in combination with etoposide and platinum (EP) in patients (pts) with untreated extensive-stage small-cell lung cancer (ED-SCLC)","volume":"28","author":"Daniel","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/S1470-2045(15)70051-3","article-title":"Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: A five-arm ph","volume":"16","author":"Melichar","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"S261","DOI":"10.1016\/j.jtho.2016.11.253","article-title":"OA05.05 Randomized phase 2 study: Alisertib (mln8237) or placebo + paclitaxel as second-line therapy for small-cell lung cancer (SCLC)","volume":"12","author":"Owonikoko","year":"2017","journal-title":"J. Thorac. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.lungcan.2016.04.014","article-title":"A phase I trial of the Hedgehog inhibitor, sonidegib (LDE225), in combination with etoposide and cisplatin for the initial treatment of extensive stage small cell lung cancer","volume":"99","author":"Pietanza","year":"2016","journal-title":"Lung Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1002\/cncr.30062","article-title":"Vismodegib or cixutumumab in combination with standard chemotherapy for patients with extensive-stage small cell lung cancer: A trial of the ECOG-ACRIN cancer research group (E1508)","volume":"122","author":"Belani","year":"2016","journal-title":"Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5900","DOI":"10.1158\/1078-0432.CCR-10-0802","article-title":"Phase II study of everolimus (RAD001) in previously treated small cell lung cancer","volume":"16","author":"Tarhini","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1038\/bjc.2013.467","article-title":"A phase-1b study of everolimus plus paclitaxel in patients with small-cell lung cancer","volume":"109","author":"Sun","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1093\/annonc\/mdt535","article-title":"A phase ib dose-escalation study of everolimus combined with cisplatin and etoposide as first-line therapy in patients with extensive-stage small-cell lung cancer","volume":"25","author":"Besse","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1634\/theoncologist.2016-0220","article-title":"A randomized phase ii study of linsitinib (OSI-906) versus topotecan in patients with relapsed small-cell lung cancer","volume":"21","author":"Chiappori","year":"2016","journal-title":"Oncologist"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.cllc.2016.09.002","article-title":"Phase 1\/2 Study of the CD56-targeting antibody-drug conjugate lorvotuzumab mertansine (IMGN901) in combination with carboplatin\/etoposide in small-cell lung cancer patients with extensive-stage disease","volume":"18","author":"Socinski","year":"2017","journal-title":"Clin. Lung Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S1470-2045(16)30565-4","article-title":"Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: A first-in-human, first-in-class, open-label, phase 1 study","volume":"18","author":"Rudin","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5711","DOI":"10.1158\/1078-0432.CCR-17-0933","article-title":"Therapy of small cell lung cancer (SCLC) with a topoisomerase-i\u2013inhibiting antibody\u2013drug conjugate (ADC) targeting trop-2, sacituzumab govitecan","volume":"23","author":"Gray","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1097\/CAD.0000000000000281","article-title":"Cyclophosphamide and tucotuzumab (huKS-IL2) following first-line chemotherapy in responding patients with extensive-disease small-cell lung cancer","volume":"26","author":"Gladkov","year":"2015","journal-title":"Anticancer Drugs"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1200\/JCO.2007.14.3461","article-title":"Randomized phase II study of carboplatin and etoposide with or without the bcl-2 antisense oligonucleotide oblimersen for extensive-stage small-cell lung cancer: CALGB 30103","volume":"26","author":"Rudin","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.1158\/1078-0432.CCR-11-3090","article-title":"Phase II study of single-agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer","volume":"18","author":"Rudin","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_94","first-page":"2014","article-title":"A phase 1 dose-escalation study of veliparib combined with carboplatin and etoposide in patients with extensive-stage small cell lung cancer and other solid tumors","volume":"25","author":"Atrafi","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1200\/JCO.18.00264","article-title":"Randomized phase II trial of cisplatin and etoposide in combination with veliparib or placebo for extensive-stage small-cell lung cancer: ECOG-ACRIN 2511 study","volume":"37","author":"Owonikoko","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1200\/JCO.2018.77.7672","article-title":"Randomized, double-blind, phase II study of temozolomide in combination with either veliparib or placebo in patients with relapsed-sensitive or refractory small-cell lung cancer","volume":"36","author":"Pietanza","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4827","DOI":"10.1182\/blood-2009-03-207316","article-title":"Flipping the wound that doesn\u2019t heal: The upside of coagulation in cancer","volume":"113","author":"Teicher","year":"2009","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Manzo, A., Montanino, A., Carillio, G., Costanzo, R., Sandomenico, C., Normanno, N., Piccirillo, M.C., Daniele, G., Perrone, F., and Rocco, G. (2017). Angiogenesis inhibitors in NSCLC. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18102021"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3967","DOI":"10.1038\/s41388-018-0213-4","article-title":"NGR (Asn-Gly-Arg)-targeted delivery of coagulase to tumor vasculature arrests cancer cell growth","volume":"37","author":"Seidi","year":"2018","journal-title":"Oncogene"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s001099900019","article-title":"Molecular and biological properties of vascular endothelial growth factor","volume":"77","author":"Ferrara","year":"1999","journal-title":"J. Mol. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/(SICI)1097-0215(19980417)79:2<144::AID-IJC8>3.0.CO;2-T","article-title":"High pre-treatment serum level of vascular endothelial growth factor (VEGF) is associated with poor outcome in small-cell lung cancer","volume":"79","author":"Salven","year":"1998","journal-title":"Int. J. Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/sj.bjc.6600130","article-title":"A high vascular count and overexpression of vascular endothelial growth factor are associated with unfavourable prognosis in operated small cell lung carcinoma","volume":"86","author":"Fontanini","year":"2002","journal-title":"Br. J. Cancer"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s10434-001-0072-y","article-title":"Vascular endothelial growth factor expression in stage I non-small cell lung cancer correlates with neoangiogenesis and a poor prognosis","volume":"8","author":"Han","year":"2001","journal-title":"Ann. Surg. Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1054\/bjoc.1999.1129","article-title":"Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer","volume":"82","author":"Koukourakis","year":"2000","journal-title":"Br. J. Cancer"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/1097-0215(20001120)89:6<475::AID-IJC2>3.0.CO;2-T","article-title":"Correlation of total VEGF mRNA and protein expression with histologic type, tumor angiogenesis, patient survival and timing of relapse in non-small-cell lung cancer","volume":"89","author":"Yuan","year":"2000","journal-title":"Int. J. Cancer"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1056\/NEJMoa061884","article-title":"Paclitaxel\u2013carboplatin alone or with bevacizumab for non\u2013small-cell lung cancer","volume":"355","author":"Sandler","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1097\/JTO.0b013e3181da36f4","article-title":"Treatment outcomes by tumor histology in eastern cooperative group study E4599 of bevacizumab with paclitaxel\/carboplatin for advanced non-small cell lung cancer","volume":"5","author":"Sandler","year":"2010","journal-title":"J. Thorac. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1200\/JCO.2007.14.5466","article-title":"Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAiL","volume":"27","author":"Reck","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.lungcan.2017.07.038","article-title":"Outcomes in patients with aggressive or refractory disease from REVEL: A randomized phase III study of docetaxel with ramucirumab or placebo for second-line treatment of stage IV non-small-cell lung cancer","volume":"112","author":"Reck","year":"2017","journal-title":"Lung Cancer"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.1158\/0008-5472.CAN-17-2176","article-title":"Combined VEGF and PD-L1 blockade displays synergistic treatment effects in an autochthonous mouse model of small cell lung cancer","volume":"78","author":"Meder","year":"2018","journal-title":"Cancer Res."},{"key":"ref_111","first-page":"539","article-title":"A novel in vitro assay for human angiogenesis","volume":"75","author":"Brown","year":"1996","journal-title":"Lab. Invest."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1097\/JTO.0000000000000089","article-title":"Characterization of fibroblast growth factor receptor 1 in small-cell lung cancer","volume":"9","author":"Thomas","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Hu, M., Hu, Y., He, J., and Li, B. (2016). Prognostic value of basic fibroblast growth factor (bFGF) in lung cancer: A systematic review with meta-analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147374"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"16052","DOI":"10.18632\/oncotarget.14109","article-title":"Inhibition of the fibroblast growth factor receptor (FGFR) pathway: The current landscape and barriers to clinical application","volume":"8","author":"Chae","year":"2017","journal-title":"Oncotarget"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1093\/annonc\/mdu390","article-title":"Phase I\/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors","volume":"25","author":"Soria","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1007\/s10637-017-0514-4","article-title":"Safety, pharmacokinetic, and pharmacodynamics of erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, in patients with advanced or refractory solid tumors","volume":"36","author":"Nishina","year":"2018","journal-title":"Invest. New Drugs"},{"key":"ref_117","first-page":"1","article-title":"TAS-120 cancer target binding; defining reactivity and revealing the first FGFR1 irreversible structure","volume":"1","author":"Kalyukina","year":"2019","journal-title":"Chem. Med. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"5033","DOI":"10.3748\/wjg.v22.i21.5033","article-title":"125I-labeled anti-bFGF monoclonal antibody inhibits growth of hepatocellular carcinoma","volume":"22","author":"Hu","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_119","first-page":"1535","article-title":"Effect of basic fibroblast growth factor antibody combined with irinotecan on proliferation and apoptosis of small cell lung cancer H223 cells in vitro","volume":"37","author":"Liao","year":"2017","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"4015","DOI":"10.3892\/mmr.2017.7099","article-title":"Production of bFGF monoclonal antibody and its inhibition of metastasis in Lewis lung carcinoma","volume":"16","author":"Yang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"4082","DOI":"10.1073\/pnas.91.9.4082","article-title":"Thalidomide is an inhibitor of angiogenesis","volume":"91","author":"Loughnan","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1006\/exer.1997.0292","article-title":"Effects of thalidomide and related metabolites in a mouse corneal model of neovascularization","volume":"64","author":"Kenyon","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/PPO.0000000000000354","article-title":"Mechanism of action and novel imid-based compounds and combinations in multiple myeloma","volume":"25","author":"Nooka","year":"2019","journal-title":"Cancer J."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1080\/13543784.2017.1313230","article-title":"Lenalidomide in the treatment of chronic lymphocytic leukemia","volume":"26","author":"Itchaki","year":"2017","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1084\/jem.182.5.1545","article-title":"Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: Inhibition by overexpression of Bcl-2 and Abl","volume":"182","author":"Martin","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"933","DOI":"10.2217\/imt.11.87","article-title":"Development of bavituximab, a vascular targeting agent with immune-modulating properties, for lung cancer treatment","volume":"3","author":"DeRose","year":"2011","journal-title":"Immunotherapy"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1093\/annonc\/mdy177","article-title":"Randomized phase III study of docetaxel plus bavituximab in previously treated advanced non-squamous non-small-cell lung cancer","volume":"29","author":"Gerber","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/j.1349-7006.2010.01826.x","article-title":"Aminopeptidase N (CD13) as a target for cancer chemotherapy","volume":"102","author":"Larsson","year":"2011","journal-title":"Cancer Sci."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1073\/pnas.1120790109","article-title":"Cooperative effects of aminopeptidase N (CD13) expressed by nonmalignant and cancer cells within the tumor microenvironment","volume":"109","author":"Rangel","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1158\/1078-0432.CCR-06-0338","article-title":"Clinical significance of aminopeptidase N in non-small cell lung cancer","volume":"12","author":"Tokuhara","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_131","first-page":"1503","article-title":"Clinical significance of aminopeptidase N\/CD13 expression in human pancreatic carcinoma","volume":"9","author":"Ikeda","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1053\/gast.2002.31095","article-title":"Aminopeptidase N is involved in cell motility and angiogenesis: Its clinical significance in human colon cancer","volume":"122","author":"Hashida","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1136\/ijgc-00009577-200609000-00010","article-title":"Expression of aminopeptidase N\/CD13 in human ovarian cancers","volume":"16","author":"Surowiak","year":"2006","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s11748-009-0445-x","article-title":"Stromal aminopeptidase N expression: Correlation with angiogenesis in non-small-cell lung cancer","volume":"57","author":"Ito","year":"2009","journal-title":"Gen. Thorac. Cardiovasc. Surg."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Schmidt, L.H., Brand, C., Stucke-Ring, J., Schliemann, C., Kessler, T., Harrach, S., Mohr, M., G\u00f6rlich, D., Marra, A., and Hillejan, L. (2017). Potential therapeutic impact of CD13 expression in non-small cell lung cancer. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0183201"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"5019","DOI":"10.1182\/blood-2008-04-150318","article-title":"Infarction of tumor vessels by NGR-peptide-directed targeting of tissue factor: Experimental results and first-in-man experience","volume":"113","author":"Bieker","year":"2009","journal-title":"Blood"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2174\/157016308783769487","article-title":"Generation of fusion proteins for selective occlusion of tumor vessels","volume":"5","author":"Kessler","year":"2008","journal-title":"Curr. Drug Discov. Technol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"S143","DOI":"10.1016\/S0049-3848(10)70033-5","article-title":"Tissue-factor fusion proteins induce occlusion of tumor vessels","volume":"125","author":"Kessler","year":"2010","journal-title":"Thromb. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1021\/jm301669z","article-title":"Anticancer therapy by tumor vessel infarction with polyethylene glycol conjugated retargeted tissue factor","volume":"56","author":"Zerbst","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"3749","DOI":"10.1021\/acs.molpharmaceut.5b00508","article-title":"Tumor growth inhibition via occlusion of tumor vasculature induced by N-terminally pegylated retargeted tissue factor tTF-NGR","volume":"12","author":"Brand","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"82458","DOI":"10.18632\/oncotarget.12559","article-title":"Combinatorial effects of doxorubicin and retargeted tissue factor by intratumoral entrapment of doxorubicin and proapoptotic increase of tumor vascular infarction","volume":"7","author":"Ronnacker","year":"2016","journal-title":"Oncotarget"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.tranon.2018.08.004","article-title":"Aminopeptidase N (CD13): Expression, Prognostic impact, and use as therapeutic target for tissue factor induced tumor vascular infarction in soft tissue sarcoma","volume":"11","author":"Kessler","year":"2018","journal-title":"Transl. Oncol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.lungcan.2017.09.013","article-title":"CD13 as target for tissue factor induced tumor vascular infarction in small cell lung cancer","volume":"113","author":"Schmidt","year":"2017","journal-title":"Lung Cancer"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"17448","DOI":"10.1073\/pnas.0508888102","article-title":"Small molecules that reactivate p53 in renal cell carcinoma reveal a NF- B-dependent mechanism of p53 suppression in tumors","volume":"102","author":"Gurova","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1002\/cmdc.201100476","article-title":"Curaxins: a new family of non-genotoxic multitargeted anticancer agents","volume":"6","author":"DiBussolo","year":"2011","journal-title":"Chem. Med. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1158\/0008-5472.CAN-17-1920","article-title":"The fact inhibitor cbl0137 synergizes with cisplatin in small-cell lung cancer by increasing notch1 expression and targeting tumor-initiating cells","volume":"78","author":"De","year":"2018","journal-title":"Cancer Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1093\/annonc\/mdx357","article-title":"Antitumor activity of lurbinectedin (PM01183) and doxorubicin in relapsed small-cell lung cancer: Results from a phase I study","volume":"28","author":"Calvo","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"7509","DOI":"10.1200\/jco.2015.33.15_suppl.7509","article-title":"Lurbinectedin (PM01183) with doxorubicin (DOX), an active treatment as second-line therapy in small cell lung cancer (SCLC)","volume":"33","author":"Forster","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/nature22323","article-title":"Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer","volume":"545","author":"Lim","year":"2017","journal-title":"Nature"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Smith, D.C., Chugh, R., Patnaik, A., Papadopoulos, K.P., Wang, M., Kapoun, A.M., Xu, L., Dupont, J., Stagg, R.J., and Tolcher, A. (2018). A phase 1 dose escalation and expansion study of Tarextumab (OMP-59R5) in patients with solid tumors. Invest. New Drugs, 1\u20139.","DOI":"10.1007\/s10637-018-0714-6"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"8564","DOI":"10.1200\/JCO.2016.34.15_suppl.8564","article-title":"Updated results of phase 1b study of tarextumab (TRXT, anti-Notch2\/3) in combination with etoposide and platinum (EP) in patients (pts) with untreated extensive-stage small-cell lung cancer (ED-SCLC)","volume":"34","author":"Chiang","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"21931","DOI":"10.1073\/pnas.1016071107","article-title":"Histone H3K27ac separates active from poised enhancers and predicts developmental state","volume":"107","author":"Creyghton","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1158\/2159-8290.CD-18-0385","article-title":"Crebbp loss drives small cell lung cancer and increases sensitivity to HDAC inhibition","volume":"8","author":"Jia","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1158\/1078-0432.CCR-07-2179","article-title":"Aurora kinases as anticancer drug targets","volume":"14","author":"Gautschi","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1158\/1535-7163.MCT-16-0298","article-title":"Barasertib (AZD1152), a Small molecule aurora b inhibitor, inhibits the growth of SCLC cell lines in vitro and in vivo","volume":"15","author":"Helfrich","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1158\/2159-8290.CD-18-0389","article-title":"Cells lacking the RB1 tumor suppressor gene are hyperdependent on Aurora B kinase for survival","volume":"9","author":"Oser","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/nrm3567","article-title":"Molecular mechanisms underlying RB protein function","volume":"14","author":"Dick","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1038\/nm.2473","article-title":"A crucial requirement for Hedgehog signaling in small cell lung cancer","volume":"17","author":"Park","year":"2011","journal-title":"Nat. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"5544","DOI":"10.1038\/onc.2017.173","article-title":"The role of canonical and non-canonical Hedgehog signaling in tumor progression in a mouse model of small cell lung cancer","volume":"36","author":"Szczepny","year":"2017","journal-title":"Oncogene"},{"key":"ref_160","first-page":"1133","article-title":"Arsenic trioxide inhibits cancer stem-like cells via down-regulation of Gli1 in lung cancer","volume":"8","author":"Chang","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_161","first-page":"2846","article-title":"Elevated expression of SOX2 and FGFR1 in correlation with poor prognosis in patients with small cell lung cancer","volume":"6","author":"Yang","year":"2013","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_162","first-page":"172","article-title":"The role of SOX2 in small cell lung cancer, lung adenocarcinoma and squamous cell carcinoma of the lung","volume":"2","author":"Karachaliou","year":"2013","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/2001-1326-3-19","article-title":"SOX2 and cancer: Current research and its implications in the clinic","volume":"3","author":"Weina","year":"2014","journal-title":"Clin. Transl. Med."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Coe, B.P., Thu, K.L., Aviel-Ronen, S., Vucic, E.A., Gazdar, A.F., Lam, S., Tsao, M.S., and Lam, W.L. (2013). Genomic deregulation of the E2F\/RB pathway leads to activation of the oncogene EZH2 in small cell lung cancer. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071670"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"5869","DOI":"10.1038\/onc.2015.38","article-title":"DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2","volume":"34","author":"Poirier","year":"2015","journal-title":"Oncogene"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1002\/ijc.29858","article-title":"Organ-specific efficacy of HSP90 inhibitor in multiple-organ metastasis model of chemorefractory small cell lung cancer","volume":"138","author":"Takeuchi","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"5120","DOI":"10.1158\/1078-0432.CCR-15-3068","article-title":"A novel HSP90 inhibitor-drug conjugate to SN38 is highly effective in small cell lung cancer","volume":"22","author":"Gaponova","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/sj.onc.1201956","article-title":"PTEN\/MMAC1 mutations identified in small cell, but not in non-small cell lung cancers","volume":"17","author":"Yokomizo","year":"1998","journal-title":"Oncogene"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.lungcan.2018.11.014","article-title":"Genetic Profiling-Based Prognostic Prediction of Patients with Advanced Small-Cell Lung Cancer in Large Scale Analysis","volume":"126","author":"Udagawa","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1200\/JCO.2009.25.3641","article-title":"The PI3K pathway as drug target in human cancer","volume":"28","author":"Courtney","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1038\/bjc.2013.474","article-title":"A multicenter phase 1 study of PX-866 in combination with docetaxel in patients with advanced solid tumours","volume":"109","author":"Bowles","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1097\/JTO.0000000000000183","article-title":"A randomized, phase 2 trial of docetaxel with or without PX-866, an irreversible oral phosphatidylinositol 3-kinase inhibitor, in patients with relapsed or metastatic non-small-cell lung cancer","volume":"9","author":"Levy","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3109\/08977194.2015.1088533","article-title":"Increased insulin-like growth factor 1 receptor (IGF1R) expression in small cell lung cancer and the effect of inhibition of IGF1R expression by RNAi on growth of human small cell lung cancer NCI-H446 cell","volume":"33","author":"Wang","year":"2015","journal-title":"Growth Factors"},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Cao, H., Dong, W., Shen, H., Xu, J., Zhu, L., Liu, Q., and Du, J. (2015). Combinational therapy enhances the effects of anti-IGF-1R mAb figitumumab to target small cell lung cancer. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135844"},{"key":"ref_175","first-page":"2511","article-title":"Autocrine function for insulin-like growth factor i in human small cell lung cancer cell lines and fresh tumor cells","volume":"50","author":"Macaulay","year":"1990","journal-title":"Cancer Res."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1158\/1535-7163.MCT-12-1067","article-title":"IGF-1R Targeting increases the antitumor effects of DNA-damaging agents in SCLC model: An opportunity to increase the efficacy of standard therapy","volume":"12","author":"Ferte","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1158\/1078-0432.CCR-15-2301","article-title":"A phase I clinical trial and independent patient-derived xenograft study of combined targeted treatment with dacomitinib and figitumumab in advanced solid tumors","volume":"23","author":"Calvo","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/annonc\/mdu517","article-title":"Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer","volume":"26","author":"Scagliotti","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/nrclinonc.2017.71","article-title":"Unravelling the biology of SCLC: Implications for therapy","volume":"14","author":"Sabari","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nrc2130","article-title":"The delta paradox: DLL4 blockade leads to more tumour vessels but less tumour growth","volume":"7","author":"Thurston","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"28989","DOI":"10.18632\/oncotarget.25615","article-title":"The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target","volume":"9","author":"Goldenberg","year":"2018","journal-title":"Oncotarget"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"556","DOI":"10.4161\/mabs.27756","article-title":"Lorvotuzumab mertansine, a CD56-targeting antibody-drug conjugate with potent antitumor activity against small cell lung cancer in human xenograft models","volume":"6","author":"Whiteman","year":"2014","journal-title":"MAbs"},{"key":"ref_183","first-page":"1","article-title":"The interplay between NCAM and FGFR signalling underlies ovarian cancer progression","volume":"5","author":"Colombo","year":"2011","journal-title":"Ecancermedicalscience"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"5197","DOI":"10.18632\/oncotarget.23708","article-title":"Promiximab-duocarmycin, a new CD56 antibody-drug conjugates, is highly efficacious in small cell lung cancer xenograft models","volume":"9","author":"Yu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1080\/1061186X.2018.1450413","article-title":"Preparation and anti-cancer evaluation of promiximab-MMAE, an anti-CD56 antibody drug conjugate, in small cell lung cancer cell line xenograft models","volume":"26","author":"Yu","year":"2018","journal-title":"J. Drug Target."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"3686","DOI":"10.1038\/s41388-018-0187-2","article-title":"Antitumor activity of CD56-chimeric antigen receptor T cells in neuroblastoma and SCLC models","volume":"37","author":"Crossland","year":"2018","journal-title":"Oncogene"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"302ra136","DOI":"10.1126\/scitranslmed.aac9459","article-title":"A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo","volume":"7","author":"Saunders","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s40268-018-0247-7","article-title":"Rovalpituzumab tesirine: A novel DLL3-targeting antibody\u2013drug conjugate","volume":"18","author":"Lashari","year":"2018","journal-title":"Drugs RD"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"3931","DOI":"10.1158\/0008-5472.CAN-17-0299","article-title":"Noninvasive interrogation of DLL3 expression in metastatic small cell lung cancer","volume":"77","author":"Sharma","year":"2017","journal-title":"Cancer Res."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1158\/1535-7163.MCT-12-0640","article-title":"Dll4-Fc, an inhibitor of Dll4-notch signaling, suppresses liver metastasis of small cell lung cancer cells through the downregulation of the NF- B activity","volume":"11","author":"Kuramoto","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1158\/1535-7163.MCT-11-1027","article-title":"MEDI0639: A novel therapeutic antibody targeting Dll4 modulates endothelial cell function and angiogenesis in vivo","volume":"11","author":"Jenkins","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.1200\/jco.2015.33.15_suppl.3024","article-title":"Phase I study of MEDI0639 in patients with advanced solid tumors","volume":"33","author":"Falchook","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"S971","DOI":"10.1016\/j.jtho.2018.08.1826","article-title":"P3.12-03 targeting DLL3 with AMG 757, a BiTE\u00ae antibody construct, and AMG 119, a CAR-T, for the treatment of SCLC","volume":"13","author":"Giffin","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1200\/JCO.2016.72.1894","article-title":"Therapy of advanced Non-Small-cell lung cancer with an SN-38-Anti-Trop-2 drug conjugate, sacituzumab govitecan","volume":"35","author":"Heist","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.celrep.2016.06.021","article-title":"Identification and targeting of long-term tumor-propagating cells in small cell lung cancer","volume":"16","author":"Jahchan","year":"2016","journal-title":"Cell Rep."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1158\/0008-5472.CAN-13-1541","article-title":"CD133+ cancer stem-like cells in small cell lung cancer are highly tumorigenic and chemoresistant but sensitive to a novel neuropeptide antagonist","volume":"74","author":"Sarvi","year":"2014","journal-title":"Cancer Res."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1133-e112","DOI":"10.1634\/theoncologist.2018-0292","article-title":"NGR-hTNF and doxorubicin as second-line treatment of patients with small cell lung cancer","volume":"23","author":"Gregorc","year":"2018","journal-title":"Oncologist"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1038\/sj.onc.1204294","article-title":"Tumor suppression and potentiation by manipulation of pp32 expression","volume":"20","author":"Bai","year":"2001","journal-title":"Oncogene"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0092-8674(04)00046-7","article-title":"Cell death: Critical control points","volume":"116","author":"Danial","year":"2004","journal-title":"Cell"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1101\/gad.13.15.1899","article-title":"BCL-2 family members and the mitochondria in apoptosis","volume":"13","author":"Gross","year":"1999","journal-title":"Genes Dev."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.tibs.2013.12.006","article-title":"Many players in BCL-2 family affairs","volume":"39","author":"Moldoveanu","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_202","first-page":"104","article-title":"Mechanisms of action of Bcl-2 family proteins","volume":"5","author":"Kale","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0169-5002(01)00290-2","article-title":"Bcl-2 is an independent prognostic factor and adds to a biological model for predicting outcome in operable non-small cell lung cancer","volume":"34","author":"Cox","year":"2001","journal-title":"Lung Cancer"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.lungcan.2005.12.009","article-title":"Expression and prognostic implications of apoptosis-related proteins in locally unresectable non-small cell lung cancers","volume":"52","author":"Fokkema","year":"2006","journal-title":"Lung Cancer"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/S0959-8049(97)10145-9","article-title":"Bcl2 and p53 regulate vascular endothelial growth factor (VEGF)-mediated angiogenesis in non-small cell lung carcinoma","volume":"34","author":"Fontanini","year":"1998","journal-title":"Eur. J. Cancer"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.lungcan.2009.06.003","article-title":"Expression of Bcl-2 predicts outcome in locally advanced non-small cell lung cancer patients treated with cisplatin-based concurrent chemoradiotherapy","volume":"68","author":"Jeong","year":"2010","journal-title":"Lung Cancer"},{"key":"ref_207","first-page":"915","article-title":"Bcl-2 and p53 protein expression in non-small cell lung cancers: correlation with survival time","volume":"2","author":"Ohsaki","year":"1996","journal-title":"Clin. Cancer Res."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1365-2559.2004.01750.x","article-title":"Prognostic value of immunohistochemical expression of p53, bax, Bcl-2 and Bcl-xL in resected non-small-cell lung cancers","volume":"44","author":"Groeger","year":"2004","journal-title":"Histopathology"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0169-5002(98)00086-5","article-title":"The interactive effect of Ras, HER2, P53 and Bcl-2 expression in predicting the survival of non-small cell lung cancer patients","volume":"22","author":"Kim","year":"1998","journal-title":"Lung Cancer"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1378\/chest.123.6.1858","article-title":"Risk of recurrence in patients with surgically resected stage I non-small cell lung carcinoma: Histopathologic and immunohistochemical analysis","volume":"123","author":"Poleri","year":"2003","journal-title":"Chest"},{"key":"ref_211","first-page":"1036","article-title":"Small cell carcinomas of the lung express the Bcl-2 protein","volume":"145","author":"Kornstein","year":"1994","journal-title":"Am. J. Pathol."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/path.1711770206","article-title":"Expression of bcl-2 oncogene protein is prevalent in small cell lung carcinomas","volume":"177","author":"Jiang","year":"1995","journal-title":"J. Pathol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.lungcan.2018.08.021","article-title":"Bcl-2 expression in circulating tumor cells (CTCs) of patients with small cell lung cancer (SCLC) receiving front-line treatment","volume":"124","author":"Messaritakis","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_214","first-page":"1","article-title":"Targeting the differential addiction to anti-apoptotic BCL-2 family for cancer therapy","volume":"8","author":"Jeng","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"218","DOI":"10.18632\/oncoscience.455","article-title":"BCL-2 inhibition is a promising therapeutic strategy for small cell lung cancer","volume":"5","author":"Lochmann","year":"2018","journal-title":"Oncoscience"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1158\/1078-0432.CCR-17-1606","article-title":"Venetoclax is effective in small-cell lung cancers with high BCL-2 expression","volume":"24","author":"Lochmann","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1158\/1535-7163.MCT-15-0885","article-title":"Inhibition of PI3K\/BMX cell survival pathway sensitizes to BH3 mimetics in SCLC","volume":"15","author":"Potter","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1158\/0008-5472.CAN-13-3460","article-title":"Rapamycin rescues ABT-737 efficacy in small cell lung cancer","volume":"74","author":"Gardner","year":"2014","journal-title":"Cancer Res."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/15384047.2015.1108485","article-title":"Combination with vorinostat overcomes ABT-263 (navitoclax) resistance of small cell lung cancer","volume":"17","author":"Nakajima","year":"2016","journal-title":"Cancer Biol. Ther."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"77378","DOI":"10.18632\/oncotarget.12671","article-title":"MYCL is a target of a BET bromodomain inhibitor, JQ1, on growth suppression efficacy in small cell lung cancer cells","volume":"7","author":"Kato","year":"2016","journal-title":"Oncotarget"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s11912-019-0762-x","article-title":"BET and EZH2 inhibitors: Novel approaches for targeting cancer","volume":"21","author":"Genta","year":"2019","journal-title":"Curr. Oncol. Rep."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"86312","DOI":"10.18632\/oncotarget.21146","article-title":"JQ1 synergizes with the Bcl-2 inhibitor ABT-263 against MYCN -amplified small cell lung cancer","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_223","doi-asserted-by":"crossref","unstructured":"Lam, L.T., Lin, X., Faivre, E.J., Yang, Z., Huang, X., Wilcox, D.M., Bellin, R.J., Jin, S., Tahir, S.K., and Mitten, M. (2017). Vulnerability of small-cell lung cancer to apoptosis induced by the combination of bet bromodomain proteins and BCL2 inhibitors. Mol. Cancer Ther., 1511\u20131521.","DOI":"10.1158\/1535-7163.MCT-16-0459"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1200\/JCO.2018.36.15_suppl.2510","article-title":"Results of the first-in-human study of ABBV-075 (mivebresib), a pan-inhibitor of bromodomain (BD) and extra terminal (BET) proteins, in patients (pts) with relapsed\/refractory (R\/R) solid tumors","volume":"36","author":"Sachdev","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.drudis.2017.09.011","article-title":"Targeting the cancer epigenome: synergistic therapy with bromodomain inhibitors","volume":"23","author":"Ramadoss","year":"2018","journal-title":"Drug Discov. Today"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1158\/2159-8290.CD-12-0112","article-title":"Proteomic profiling identifies dysregulated pathways in small cell lung cancer and novel therapeutic targets including PARP1","volume":"2","author":"Byers","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ejmech.2019.01.024","article-title":"Medicinal chemistry approaches of poly ADP-Ribose polymerase 1 (PARP1) inhibitors as anticancer agents\u2014A recent update","volume":"165","author":"Jain","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1158\/1078-0432.CCR-16-1040","article-title":"PARP inhibitor activity correlates with SLFN11 expression and demonstrates synergy with temozolomide in small cell lung cancer","volume":"23","author":"Lok","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12967-017-1296-3","article-title":"Report on the first SLFN11 monothematic workshop: From function to role as a biomarker in cancer","volume":"15","author":"Ballestrero","year":"2017","journal-title":"J. Transl. Med."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.ccell.2017.01.006","article-title":"Chemosensitive relapse in small cell lung cancer proceeds through an EZH2-SLFN11 Axis","volume":"31","author":"Gardner","year":"2017","journal-title":"Cancer Cell"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/5\/690\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:53:07Z","timestamp":1760187187000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/5\/690"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,17]]},"references-count":230,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["cancers11050690"],"URL":"https:\/\/doi.org\/10.3390\/cancers11050690","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,17]]}}}