Small cell lung cancer

an overview of the targets

Autores

  • Bruna Nardy Valadares Immunobiological and Biopharmaceutical Laboratory, Pharmaceutical-Biochemistry Technology Department, School of Pharmaceutical Science, São Paulo University, São Paulo, Brazil
  • Marco Antonio Stephano Immunobiological and Biopharmaceutical Laboratory, Pharmaceutical-Biochemistry Technology Department, School of Pharmaceutical Science, São Paulo University, São Paulo, Brazil

DOI:

https://doi.org/10.1590/s2175-97902022e19114

Palavras-chave:

Small cell lung cancer. Targeted therapies. Immunotherapy. Apoptosis. DLL-3. Receptor tyrosine kinase inhibitors.

Resumo

Lung cancer is the leading cause of cancer deaths worldwide. Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases. Despite a frequently good response to first-line treatment with chemotherapy and/or radiotherapy, early relapse occurs in the majority of patients and 5-year survival is only about 5%. This histological subtype of lung cancer is strongly associated with tobacco smoking. The behavior of SCLC is unique within solid tumors. Initially, it positively responds to chemotherapy or radiotherapy. However, at relapse, which occurs early in the majority of cases, the tumor is resistant to available therapy and eventually will cause the death of the patient. These results in an overall 5-year survival of approximately 5% for the entire population of patients diagnosed with SCLC. This dismal prognosis has not significantly changed in past years. There is an urgent need for discovery targets to select patients more prone to having a proper response to the treatment, avoiding to reduce their resistance and resulting the increase of overall and progression-free survivals.

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Referências

Allen JW, Moon J, Redman M, Gadgeel SM, Kelly K, Mack PC, et al. Southwest Oncology Group S0802: a randomized, phase II trial of weekly topotecan with and without zivaflibercept in patients with platinum-treated small-cell lung cancer. J Clin Oncol. 2014;32(23):2463-70.

Arcaro A. Involvement of autophagy in the response of tumor cells to PtdIns3K inhibitors: therapeutic implications. Autophagy. 2013;9(4):607-8.

Arriola E, Cañadas I, Arumí M, Dómine M, Lopez-Vilariño JA, Arpí O, et al. MET phosphorylation predicts poor outcome in small cell lung carcinoma and its inhibition blocks HGF-induced effects in MET mutant cell lines. Br J Cancer. 2011;105(6):814-23.

Arriola E, Cañadas I, Arumí M, Rojo M, Rovira A, Albanell J. Genetic changes in small cell lung carcinoma. Clin Transl Oncol. 2008;10(4):189-97.

Badzio A, Wynes MW, Dziadziuszko R, Merrick DT, Pardo M, Rzyman W, et al. Increased insulin-like growth factor 1 receptor protein expression and gene copy number in small cell lung cancer. J Thorac Oncol. 2010;5(12):1905-11.

Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 2006;5(9):769-84.

Byers LA, Wang J, Nilsson MB, Fujimoto J, Saintigny P, Yordy J, et al. Proteomic profiling identifies dysregulated pathways in small cell lung cancer and novel therapeutic targets including PARP1. Cancer Discov. 2012;2(9):798-811.

Califano R, Abidin AZ, Peck R, Faivre-Finn C, Lorigan P. Management of small cell lung cancer: recent developments for optimal care. Drugs. 2012;72(4):471-90.

Castellone MD, Laukkanen MO, Teramoto H, Bellelli R, Alì G, Fontanini G, et al. Cross talk between the bombesin neuropeptide receptor and Sonic hedge-hog pathways in small cell lung carcinoma. Oncogene. 2015;34(13):1679-1687.

Camirand A, Pollak M. Co-targeting IGF-1R and c-kit: synergistic inhibition of proliferation and induction of apoptosis in H 209 small cell lung cancer cells. Br J Cancer . 2004;90(9):1825-9.

Cardnell RJ, Feng Y, Diao L, Fan YH, Masrorpour F, Wang J, et al. Proteomic markers of DNA repair and PI3K pathway activation predict response to the PARP inhibitor BMN 673 in small cell lung cancer. Clin Cancer Res. 2013;19(22):6322-8.

Carter L, Rothwell DG, Mesquita B, Smowton C, Leong HS, Fernandez-Gutierrez F, et al. Molecular analysis of circulating tumor cells identifies distinct copy-number profiles in patients with chemosensitive and chemorefractory small-cell lung cancer. Nat Med. 2017;23(1):114-119. DOI: 10.1038/nm.4239.

» https://doi.org/10.1038/nm.4239.

Churg A. Lung Biology in Health and Disease. In: Samet JM, editor. Epidemiology of Lung-Cancer. New York: Marcel Dekker Inc., 1994;413-36.

Crisanti MC, Wallace AF, Kapoor V, Vandermeers F, Dowling ML, Pereira LP, et al. The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer. Mol Cancer Ther. 2009;8(8):2221-31.

Cui M, Augert A, Rongione M, Conkrite K, Parazzoli S, Nikitin AY, et al. PTEN is a potent suppressor of small cell lung cancer. Mol Cancer Res. 2014;12(5):654-9.

Di Maio, Scagliotti GV. The lesson learned from figitumumab clinical program and the hope for better results in squamous lung cancer. Transl Lung Cancer Res. 2015;4(1):15-17. DOI: 10.3978/j.issn.2218-6751.2015.01.02.

» https://doi.org/10.3978/j.issn.2218-6751.2015.01.02.

Faber AC, Farago AF, Costa C, Dastur A, Gomez-Caraballo M, Robbins R, et al. Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer. Proc Natl Acad Sci USA. 2015;112(11):E1288-96.

Ferte C, Loriot Y, Clemenson C, Commo F, Gombos A, Bibault JE, et al. IGF-1R targeting increases the antitumor effects of DNA-damaging agents in SCLC model: an opportunity to increase the efficacy of standard therapy. Mol CancerTher. 2013;12(7):1213-22.

Freeman-Keller M, Goldman J, Gray J. Vaccine immunotherapy in lung cancer: Clinical experience and future directions. Pharmacol Ther. 2015;153:1-9.

George J, Lim JS, Jang SJ, Cun Y, Ozretić L, Kong G, et al. Comprehensive genomic profiles of small cell lung cancer. Nature. 2015;524(7563):47-53. DOI:10.1038/nature14664.

» https://doi.org/10.1038/nature14664

Hall RD, Gray JE, Chiappori AA. Beyond the standard of care: a review of novel immunotherapy trials for the treatment of lung cancer. Cancer Control. 2013;20(1):22-31.

Han JY, Kim HY, Lim KY, Han JH, Lee YJ, Kwak MH, et al. A phase II study of sunitinib in patients with relapsed or refractory small cell lung cancer. Lung Cancer. 2013;79(2):137-42.

Hendriks LE, Dingemans AC. Heat shock protein antagonists in early stage clinical trials for NSCLC. Expert Opin Investig Drugs . 2017;26(5):541-550.

Hubaux R, Vandermeers F, Crisanti MC, Kapoor V, Burny A, Mascaux C, et al. Preclinical evidence for a beneficial impact of valproate on the response of small cell lungcancer to first-line chemotherapy. Eur J Cancer. 2010;46(9):1724-34.

Ishii H, Azuma K, Kawahara A, Yamada K, Imamura Y, Tokito T, et al. Significance of programmed cell death-ligand 1 expression and its association with survival in patients with small cell lung cancer. J Thorac Oncol . 2015;10(3):426-30.

Kalemkerian GP, Akerley W, Bogner P, Borghaei H, Chow LQ, Downey RJ, et al. Small cell lung cancer. J Natl Compr Canc Netw. 2013;11(1):78-98.

Kaminskyy VO, Surova OV, Vaculova A, Zhivotovsky B. Combinedinhibition of DNA methyltransferase and histone deacetylase restorescaspase-8 expression and sensitizes SCLC cells to TRAIL. Carcino-genesis. 2011;32(10):1450-8.

Khanzada UK, Pardo OE, Meier C, Downward J, Seckl MJ, Arcaro A. Potent inhibition of small-cell lung cancer cell growth by simvastatin reveals selective functions of Ras isoforms in growth factor signalling. Oncogene . 2006;25(6):877-87.

Komarnitsky PB, Lee HJ, Shah M, Wong S, Gauthier S, Dziubinski J, et al. A phase III study of rovalpituzumab tesirine maintenance therapy following first-line platinum-based chemotherapy in patients with extensive disease small cell lung cancer (ED SCLC). J Clin Oncol . 2017;35(15 Suppl):TPS8583.

Kraus AC, Ferber I, Bachmann SO, Specht H, Wimmel A, Gross MW, et al. In vitro chemo- and radio-resistance in small cell lung cancer correlates with cell adhesion and constitutive activation of AKT and MAP kinase pathways. Oncogene . 2002;21(57):8683-95.

Krystal GW, Honsawek S, Litz J, Buchdunger E. The selective tyrosine kinase inhibitor STI571 inhibits small cell lung cancer growth. Clin Cancer Res . 2000;6(8):3319-26.

Krystal GW, Sulanke G, Litz J. Inhibition of phosphatidylinositol 3-kinase-Akt signaling blocks growth, promotes apoptosis, and enhances sensitivity of small cell lung cancer cells to chemotherapy. Mol Cancer Ther . 2002;1(11):913-22.

Litz J, Sakuntala Warshamana-Greene G, Sulanke G, Lipson KE , Krystal GW. The multi-targeted kinase inhibitor SU5416 inhibits small cell lung cancer growth and angiogenesis, in part by blocking Kit-mediated VEGF expression. Lung Cancer . 2004;46(3):283-91.

Loriot Y, Mordant P, Dugue D, Geneste O, Gombos A, Opolon P, et al. Radiosensitization by a novelBcl-2 and Bcl-XL inhibitor S44563 in small-cell lung cancer. Cell Death Dis. 2014;5(9):e1423.

Luszczek W, Cheriyath V, Mekhail TM, Borden EC. Combinations of DNA methyltransferase and histone deacetylase inhibitors induce DNA damage in small cell lung cancer cells: correlation of resistance with IFN-stimulated gene expression. Mol Cancer Ther . 2010;9(8):2309-21.

Macaulay VM, Everard MJ, Teale JD, Trott PA, Van Wyk JJ, Smith IE, et al. Autocrine function for insulin-like growth factor I in human small cell lung cancer cell lines and fresh tumor cells. Cancer Res. 1990;50(8):2511-7.

Marinov M, Ziogas A, Pardo OE, Tan LT, Dhillon T, Mauri FA, et al. AKT/mTOR pathway activation and BCL-2 family proteins modulate the sensitivity of human small cell lung cancer cells to RAD001. Clin Cancer Res . 2009;15(4):1277- 87.

Markham A. Idelalisib: first global approval. Drugs . 2014;74(14):1701-7.

Maulik G, Kijima T, Ma PC, Ghosh SK, Lin J, Shapiro GI, et al. Modulation of the c-Met/hepatocytegrowth factor pathway in small cell lung cancer. Clin Cancer Res . 2002;8(2):620-7.

Moore AM, Einhorn LH, Estes D, Govindan R, Axelson J, Vinson J, et al. Gefitinib in patients with chemo-sensitive and chemo refractory relapsed small cell cancers: a Hoosier Oncology Group phase II trial. Lung Cancer . 2006;52(1):93-7.

Neal JW, Sequist LV. Exciting new targets in lung cancer therapy: ALK, IGF-1R, HDAC, and Hh. Curr Treat Options Oncol. 2010;11(1-2):36-44.

Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. N Engl J Med. 2012;367:1792-802.

Pardo OE, Arcaro A, Salerno G, Raguz S, Downward J, Seckl MJ. Fibroblast growth factor-2 induces translational regulation of Bcl-XLand Bcl-2 via a MEK-dependent pathway: correlation with resistance nto etoposide-induced apoptosis. J Biol Chem. 2002;277(14):12040-6.

Pardo OE, Arcaro A, Salerno G, Tetley TD, Valovka T, Gout I, et al. Novel cross talk between MEK and S6K2 in FGF-2 induced proliferation of SCLC cells. Oncogene . 2001;20:7658-67.

Pardo OE, Latigo J, Jeffery RE, Nye E, Poulsom R, Spencer-Dene B, et al. The fibroblast growth factor receptor inhibitor PD173074 blocks small cell lung cancer growth in vitro and in vivo. Cancer Res. 2009;69(22):8645-51.

Park KS, Martelotto LG, Peifer M, Sos ML, Karnezis AN, Mahjoub MR, et al. A crucial requirement for Hedgehog signaling in small cell lung cancer. Nat Med. 2011;17(11):1504-8.

Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ. 2010;340:b5569.

Peifer M, Fernández-Cuesta L, Sos ML, George J, Seidel D, Kasper LH, et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet. 2012;44(10):1104-10. https://pubmed.ncbi.nlm.nih. gov/22941188/

» https://pubmed.ncbi.nlm.nih. gov/22941188/

Pesch B, Kendzia B, Gustavsson P, Jöckel KH, Johnen G, Pohlabeln H, et al. Cigarette smoking and lung cancer-relative risk estimates for the major histological types from a pooled analysis of case-control studies. Int J Cancer. 2012;131(5):1210-9.

Pietanza MC, Ladanyi M. Bringing the genomic landscape of small-cell lung cancer into focus. Nat Genet . 2012;44(10):1074-5.

Pietanza MC, Rudin CM. Novel therapeutic approaches for small cell lung cancer: the future has arrived. Curr Probl Cancer. 2012;36(3):156-73.

Platta CS, Greenblatt DY, Kunnimalaiyaan M, Chen H. The HDAC inhibitor trichostatin A inhibits growth of small cell lung cancer cells. J Surg Res. 2007;142(2):219-26.

Pujol JL, Lavole A, Quoix E, Molinier O, Souquet PJ, Barlesi F, et al. Randomized phase II-III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial. Ann Oncol. 2015;26(5):908-14. DOI: 10.1093/annonc/ mdv065.

» https://doi.org/10.1093/annonc/ mdv065.

Ramalingam S, Blais N, Mazieres J, Reck M, Jones CM, Juhasz E, et al. A Randomized, Double-Blind, Phase 2 Trial of Veliparib (ABT-888) With Carboplatin and Paclitaxel in Previously Untreated Metastatic or Advanced Non-Small Cell Lung Cancer . Metastatic Non-Small Cell Lung Cancer . 2014;90(5)-S4-S5.

Ready NE, Dudek AZ, Pang HH, et al. Cisplatin, Irinotecan, and Bevacizumab for Untreated Extensive-Stage Small-Cell Lung Cancer : CALGB 30306, a Phase II Study. J Clin Oncol . 2011;29(33):4436-4441.

Rolle CE, Kanteti R, Surati M, Nandi S, Dhanasingh I, Yala S, et al. Combined MET inhibition and topoisomerase I inhibition block cell growth of small cell lung cancer. Mol Cancer Ther . 2014;13(3):576-84.

Ross JS, Wang K, Elkadi OR, Tarasen A, Foulke L, Sheehan CE, et al. Next-generation sequencing reveals frequent consistent genomic alterations in small cell undifferentiated lung cancer. J Clin Pathol. 2014;67(9):772-6.

Rudin CM, Durinck S, Stawiski EW, Poirier JT, Modrusan Z, Shames DS, et al. Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet . 2012a;44(10):1111-6.

Rudin CM, Hann CL, Garon EB, Oliveira MR, Bonomi PD, Camidge DR, et al. Phase II study of single-agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer. Clin Cancer Res . 2012b;18(11):3163-9.

Rudin CM, Pietanza MC, Bauer TM, Ready N, Morgensztern D, Glisson BS, et al. 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. Lancet Oncol. 2017;18(1):42-51.

Rygaard K, Nakamura T, Spang-Thomsen M. Expression of the proto-oncogenes c-met and c-kit and their ligands, hepatocyte growth factor/scatter factor and stem cell factor, in SCLC cell lines and xenografts. Br J Cancer . 1993;67(1):37-46.

Sos ML, Dietlein F, Peifer M, Schöttle J, Balke-Want H, Müller C, et al. A framework for identification of actionable cancer genome dependencies in small cell lung cancer. Proc Natl Acad Sci USA. 2012;109(42):17034-9.

Spigel DR, Greco FA, Rubin MS, Shipley D, Thompson DS, Lubiner ET, et al. Phase II study of maintenance sunitinib following irinotecan and carboplatin as first-line treatment for patients with extensive-stage small-cell lung cancer. Lung Cancer . 2012;77(2):359-64. DOI: 10.1016/j. lungcan.2012.03.009.

» https://doi.org/10.1016/j. lungcan.2012.03.009.

Sun JM, Lee KH, Kim BS, Kim HG, Min YJ, Yi SY, et al. Pazopanib maintenance after first-line etoposide and platinum chemotherapy in patients with extensive disease small-cell lung cancer: a multicentre, randomised, placebo-controlled Phase II study (KCSG-LU12-07). Br J Cancer . 2018;118(5):648-653. DOI: 10.1038/bjc.2017.465.

» https://doi.org/10.1038/bjc.2017.465.

Tatematsu A, Shimizu J, Murakami Y, Horio Y, Nakamura S, Hida T, et al. Epidermal growth factor receptor mutations in small cell lung cancer. Clin Cancer Res . 2008;14(19):6092-6.

Tiseo M, Boni L, Ambrosio F, Camerini A, Baldini E, Cinieri S, et al. 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. J Clin Oncol . 2017;35(12):1281-1287. DOI: 10.1200/ JCO.2016.69.4844.

» https://doi.org/10.1200/ JCO.2016.69.4844.

Trepel J, Mollapour M, Giaccone G, Neckers L. Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer. 2010;10(8):537-49.

Tsurutani J, Soda H, Oka M, Suenaga M, Doi S, Nakamura Y, et al. Antiproliferative effects of thehistone deacetylase inhibitor FR901228 on small-cell lung cancer lines and drug-resistant sublines. J Cancer. 2003;104(2):238-42.

Umemura S, Mimaki S, Makinoshima H, Tada S, Ishii G, Ohmatsu H, et al. Therapeutic priority of the PI3K/ AKT/mTOR pathway in small cell lung cancers as revealed by a comprehensive genomic analysis. J Thorac Oncol . 2014; 9(9):1324-31.

van Meerbeeck JP, Fennell DA, De Ruysscher DK. Small cell lung cancer. Lancet. 2011;378(9804):1741-55.

Viganò MG, Cavina R, Novello S, Grossi F, Santoro A, Gregorc V, et al. Phase II trial of NGR-hTNF and doxorubicin in relapsed small cell lung cancer (SCLC). J Clin Oncol . 2011;29(15):abstr 7077.

Voortman J, Harada T, Chang RP, Killian JK, Suuriniemi M, Smith WI, et al. Detection and therapeutic implications of c-Met mutations in small cell lung cancer and neuroendocrine tumors. Curr Pharm Des. 2013;19(5):833-40.

Walls M, Baxi SM, Mehta PP, Liu KK, Zhu J, Estrella H, et al. Targeting small cell lung cancer harboring PIK3CA mutation with a selective oral PI3K inhibitor PF-4989216. Clin Cancer Res . 2014;20(3):631-43.

Wakuda K, Kenmotsu H, Serizawa M, Koh Y, Isaka M, Takahashi S, et al. Molecular profiling of small cell lung cancer in a Japanese cohort. Lung Cancer . 2014;84(2):139- 44.

Warshamana-Greene GS, Litz J, Buchdunger E, Hofmann F, Garcı́a-Echeverrı́a C, Krystal GW, et al. The insulin-like growth factor-I (IGF-I) receptor kinase inhibitor NVP-ADW742, in combination withSTI571, delineates a spectrum of dependence of small cell lung cancer on IGF-I and stem cell factor signaling. Mol Cancer Ther . 2004;3(5):527-35.

Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy PA, Baylin SB. Hedgehog signaling within airway epithelial progenitors and in small-cell lung cancer. Nature . 2003;422(6929):313-7.

Wojtalla A, Fischer B, Kotelevets N, Mauri FA, Sobek J, Rehrauer H, et al. Targeting the phosphoinositide 3-kinase p110-alpha isoform impairs cell proliferation, survival, and tumor growth in small cell lung cancer. Clin Cancer Res . 2013;19(1):96-105.

Wong KK, Engelman JA, Cantley LC. Targeting the PI3K signaling pathway in cancer. Curr Opin Genet Dev. 2010;20(1):87-90.

Yoh K, Seto T, Satouchi M, Nishio M, Yamamoto M, Murakami H, et al. Vandetanib in patients with previously treated RET-rearranged advanced non-small-cell lung cancer (LURET): an open-label, multicentre phase 2 trial. Lancet Respir Med. 2017;5(1):42-50.

Zangemeister-Wittke U, Schenker T, Luedke GH, Stahel RA. Synergistic cytotoxicity of bcl-2 antisense oligodeoxynucleotides and etoposide, doxorubicin and cisplatin on small-cell lung cancer cell lines.Br J Cancer . 1998;78(8):1035-42.

Zhan P, Wang J, Lv XJ, Wang Q, Qiu LX, Lin XQ, et al. Prognostic value of vascular endothelial growth factor expression in patients with lung cancer: a systematic review with meta-analysis. J Thorac Oncol . 2009;4(9):1094-103.

Zinn RL, Gardner EE, Marchionni L, Murphy SC, Dobromilskaya I, Hann CL, et al. ERK phosphorylation is predictive of resistance to IGF-1R inhibition in small cell lung cancer. Mol Cancer Ther . 2013;12(6):1131-9.

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2022-11-18

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Small cell lung cancer: an overview of the targets. (2022). Brazilian Journal of Pharmaceutical Sciences, 58. https://doi.org/10.1590/s2175-97902022e19114