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Therapeutic Strategies Targeting Signaling Pathways in Lung Cancer

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Targeting Cellular Signalling Pathways in Lung Diseases

Abstract

Recent knowledge of the role of signaling pathways and their underlying mechanisms in the pathogenesis of several diseases may lead to the development of therapeutic strategies. In the recent time, several drug molecules have been developed which target the cell signaling pathways and may be used in combination with other standard therapies for the synergistic effects in reducing the lung cancer pathophysiology across the world. Further, some of predictive biomarkers have been identified. The current chapter deals with the involvement of signaling pathways in the development of lung cancer and further new therapeutic approaches that intend to pave the way for the development of improved clinical treatment of lung cancer.

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References

  1. Proctor RN (2001) Tobacco and the global lung cancer epidemic. Nat Rev Cancer 1:82–86

    Article  CAS  PubMed  Google Scholar 

  2. Jemal A, Thun MJ, Ries LA, Howe HL, Weir HK, Center MM, Ward E, Wu XC, Eheman C, Anderson R, Ajani UA, Kohler B, Edwards BK (2008) Annual report to the nation on the status of cancer, 1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst 100:1672–1694

    Article  PubMed  PubMed Central  Google Scholar 

  3. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30

    Article  PubMed  Google Scholar 

  4. Weiss W (1997) Cigarette smoking and lung cancer trends. A light at the end of the tunnel? Chest 111:1414–1416

    Article  CAS  PubMed  Google Scholar 

  5. Bryant A, Cerfolio RJ (2007) Differences in epidemiology, histology, and survival between cigarette smokers and never-smokers who develop non-small cell lung cancer. Chest 132:185–192

    Article  PubMed  Google Scholar 

  6. Dutu T, Michiels S, Fouret P, Penault-Llorca F, Validire P, Benhamou S, Taranchon E, Morat L, Grunenwald D, Le Chevalier T, Sabatier L, Soria JC (2005) Differential expression of biomarkers in lung adenocarcinoma: a comparative study between smokers and never-smokers. Ann Oncol 16:1906–1914

    Article  CAS  PubMed  Google Scholar 

  7. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386

    Article  CAS  PubMed  Google Scholar 

  8. Gatta G, Mallone S, van der Zwan JM, Trama A, Siesling S, Capocaccia R, Hackl M, Van Eycken E, Henau K, Hedelin G, Velten M, Launoy G, Guizard AV, Bouvier AM, Maynadié M, Woronoff AS, Buemi A, Colonna M, Ganry O, Grosclaude P, Holleczek B, Ziegler H, Tryggvadottir L, Bellù F, Ferretti S, Serraino D, Dal Maso L, Bidoli E, Birri S, Zucchetto A, Zainer L, Vercelli M, Orengo MA, Casella C, Quaglia A, Federico M, Rashid I, Cirilli C, Fusco M, Traina A, Michiara M, De Lisi V, Bozzani F, Giacomin A, Tumino R, La Rosa MG, Spata E, Signora A, Mangone L, Falcini F, Giorgetti S, Ravaioli A, Senatore G, Iannelli A, Budroni M, Piffer S, Franchini S, Crocetti E, Caldarella A, Intrieri T, La Rosa F, Stracci F, Cassetti T, Contiero P, Tagliabue G, Zambon P, Guzzinati S, Berrino F, Baili P, Bella F, Ciampichini R, Gatta G, Margutti C, Micheli A, Minicozzi P, Sant M, Trama A, Caldora M, Capocaccia R, Carrani E, De Angelis R, Francisci S, Grande E, Inghelmann R, Lenz H, Martina L, Roazzi P, Santaquilani M, Simonetti A, Tavilla A, Verdecchia A, Langmark F, Rachtan J, Mężyk R, Góżdź S, Siudowska U, Zwierko M, Bielska-Lasota M, Safaei Diba C, Primic-Zakelj M, Mateos A, Izarzugaza I, Torrella Ramos A, Zurriaga O, Marcos-Gragera R, Vilardell ML, Izquierdo A, Ardanaz E, Moreno-Iribas C, Galceran J, Klint Å, Talbäck M, Jundt G, Usel M, Frick H, Ess SM, Bordoni A, Konzelmann I, Dehler S, Siesling S, Visser O, Otter R, Coebergh JWW, Greenberg DC, Wilkinson J, Roche M, Verne J, Meechan D, Poole J, Lawrence G, Gavin A, Brewster DH, Black RJ, Steward JA (2013) Cancer prevalence estimates in Europe at the beginning of 2000. Ann Oncol 24:1660–1666

    Article  CAS  PubMed  Google Scholar 

  9. Siegel RL, Miller KD, Jemal A (2017) Cancer Statistics, 2017. CA Cancer J Clin 67:7–30

    Article  PubMed  Google Scholar 

  10. Marx A, Chan JK, Coindre JM, Detterbeck F, Girard N, Harris NL, Jaffe ES, Kurrer MO, Marom EM, Moreira AL, Mukai K, Orazi A, Strobel P (2015) The 2015 World Health Organization classification of tumors of the thymus: continuity and changes. J Thorac Oncol 10:1383–1395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cho WC (2012) Targeting the signaling pathways in cancer therapy. Expert Opin Ther Targets 16:1–3

    Article  CAS  PubMed  Google Scholar 

  12. Brambilla E, Gazdar A (2009) Pathogenesis of lung cancer signalling pathways: roadmap for therapies. Eur Respir J 33:1485–1497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, Postmus PE, Rusch V, Sobin L (2007) The IASLC lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol 2:706–714

    Article  PubMed  Google Scholar 

  14. Smith AD, Roda D, Yap TA (2014) Strategies for modern biomarker and drug development in oncology. J Hematol Oncol 7:70

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C (2015) Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol 26:1877–1883

    Article  CAS  PubMed  Google Scholar 

  16. Xing P, Wang S, Hao X, Zhang T, Li J (2016) Clinical data from the real world: efficacy of Crizotinib in Chinese patients with advanced ALK-rearranged non-small cell lung cancer and brain metastases. Oncotarget 7:84666–84674

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sun W, Yuan X, Tian Y, Wu H, Xu H, Hu G, Wu K (2015) Non-invasive approaches to monitor EGFR-TKI treatment in non-small-cell lung cancer. J Hematol Oncol 8:95

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, Allen C, Hansen G, Woodbrook R, Wolfe C, Hamadeh RR, Moore A, Werdecker A, Gessner BD, Te Ao B, McMahon B, Karimkhani C, Yu C, Cooke GS, Schwebel DC, Carpenter DO, Pereira DM, Nash D, Kazi DS, De Leo D, Plass D, Ukwaja KN, Thurston GD, Yun Jin K, Simard EP, Mills E, Park EK, Catalá-López F, deVeber G, Gotay C, Khan G, Hosgood HD 3rd, Santos IS, Leasher JL, Singh J, Leigh J, Jonas JB, Sanabria J, Beardsley J, Jacobsen KH, Takahashi K, Franklin RC, Ronfani L, Montico M, Naldi L, Tonelli M, Geleijnse J, Petzold M, Shrime MG, Younis M, Yonemoto N, Breitborde N, Yip P, Pourmalek F, Lotufo PA, Esteghamati A, Hankey GJ, Ali R, Lunevicius R, Malekzadeh R, Dellavalle R, Weintraub R, Lucas R, Hay R, Rojas-Rueda D, Westerman R, Sepanlou SG, Nolte S, Patten S, Weichenthal S, Abera SF, Fereshtehnejad SM, Shiue I, Driscoll T, Vasankari T, Alsharif U, Rahimi-Movaghar V, Vlassov VV, Marcenes WS, Mekonnen W, Melaku YA, Yano Y, Artaman A, Campos I, MacLachlan J, Mueller U, Kim D, Trillini M, Eshrati B, Williams HC, Shibuya K, Dandona R, Murthy K, Cowie B, Amare AT, Antonio CA, Castañeda-Orjuela C, van Gool CH, Violante F, Oh IH, Deribe K, Soreide K, Knibbs L, Kereselidze M, Green M, Cardenas R, Roy N, Tillmann T, Li Y, Krueger H, Monasta L, Dey S, Sheikhbahaei S, Hafezi-Nejad N, Kumar GA, Sreeramareddy CT, Dandona L, Wang H, Vollset SE, Mokdad A, Salomon JA, Lozano R, Vos T, Forouzanfar M, Lopez A, Murray C, Naghavi M (2015) The global burden of cancer 2013. JAMA Oncol 1:505–527

    Article  PubMed  Google Scholar 

  19. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108

    Article  PubMed  Google Scholar 

  20. Goss PE, Strasser-Weippl K, Lee-Bychkovsky BL, Fan L, Li J, Chavarri-Guerra Y, Liedke PE, Pramesh CS, Badovinac-Crnjevic T, Sheikine Y, Chen Z, Qiao YL, Shao Z, Wu YL, Fan D, Chow LW, Wang J, Zhang Q, Yu S, Shen G, He J, Purushotham A, Sullivan R, Badwe R, Banavali SD, Nair R, Kumar L, Parikh P, Subramanian S, Chaturvedi P, Iyer S, Shastri SS, Digumarti R, Soto-Perez-de-Celis E, Adilbay D, Semiglazov V, Orlov S, Kaidarova D, Tsimafeyeu I, Tatishchev S, Danishevskiy KD, Hurlbert M, Vail C, St Louis J, Chan A (2014) Challenges to effective cancer control in China, India, and Russia. Lancet Oncol 15:489–538

    Article  PubMed  Google Scholar 

  21. Debakey M (1999) Carcinoma of the lung and tobacco smoking: a historical perspective. Ochsner J 1:106–108

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Hasse C (1846) Cancerous tumors in the respiratory organs. An anatomical description of the diseases of the organs of the circulation and respiration. Sydeham Society, England, London, pp 370–375

    Google Scholar 

  23. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90

    Article  PubMed  Google Scholar 

  24. Arnold M, Soerjomataram I, Ferlay J, Forman D (2015) Global incidence of oesophageal cancer by histological subtype in 2012. Gut 64:381–387

    Article  PubMed  Google Scholar 

  25. Ferlay J, Colombet M, Soerjomataram I, Dyba T, Randi G, Bettio M, Gavin A, Visser O, Bray F (2018) Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer 103:356–387

    Article  CAS  PubMed  Google Scholar 

  26. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30

    Article  PubMed  Google Scholar 

  27. Schabath MB, Cote ML (2019) Cancer progress and priorities: lung cancer. Cancer Epidemiol Biomark Prev 28:1563–1579

    Article  Google Scholar 

  28. Dela Cruz CS, Tanoue LT, Matthay RA (2011) Lung cancer: epidemiology, etiology, and prevention. Clin Chest Med 32:605–644

    Article  Google Scholar 

  29. Kohler BA, Ward E, McCarthy BJ, Schymura MJ, Ries LA, Eheman C, Jemal A, Anderson RN, Ajani UA, Edwards BK (2011) Annual report to the nation on the status of cancer, 1975-2007, featuring tumors of the brain and other nervous system. J Natl Cancer Inst 103:714–736

    Article  PubMed  PubMed Central  Google Scholar 

  30. Jemal A, Miller KD, Ma J, Siegel RL, Fedewa SA, Islami F, Devesa SS, Thun MJ (2018) Higher Lung Cancer Incidence in Young Women Than Young Men in the United States. N Engl J Med 378:1999–2009

    Article  PubMed  PubMed Central  Google Scholar 

  31. Wakelee HA, Chang ET, Gomez SL, Keegan TH, Feskanich D, Clarke CA, Holmberg L, Yong LC, Kolonel LN, Gould MK, West DW (2007) Lung cancer incidence in never smokers. J Clin Oncol 25:472–478

    Article  PubMed  Google Scholar 

  32. Forman D, de Martel C, Lacey CJ, Soerjomataram I, Lortet-Tieulent J, Bruni L, Vignat J, Ferlay J, Bray F, Plummer M (2012) Global burden of human papillomavirus and related diseases. Vaccine 30:F12–F23

    Article  PubMed  Google Scholar 

  33. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O’Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR (2007) Patterns of somatic mutation in human cancer genomes. Nature 446:153–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WE, Nicholson AG, Groome P, Mitchell A, Bolejack V (2016) The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol 11:39–51

    Article  PubMed  Google Scholar 

  35. Nesbitt JC, Putnam JB Jr, Walsh GL, Roth JA, Mountain CF (1995) Survival in early-stage non-small cell lung cancer. Ann Thorac Surg 60:466–472

    Article  CAS  PubMed  Google Scholar 

  36. Shah R, Sabanathan S, Richardson J, Mearns AJ, Goulden C (1996) Results of surgical treatment of stage I and II lung cancer. J Cardiovasc Surg 37:169–172

    CAS  Google Scholar 

  37. Walters S, Maringe C, Coleman MP, Peake MD, Butler J, Young N, Bergström S, Hanna L, Jakobsen E, Kölbeck K, Sundstrøm S, Engholm G, Gavin A, Gjerstorff ML, Hatcher J, Johannesen TB, Linklater KM, McGahan CE, Steward J, Tracey E, Turner D, Richards MA, Rachet B (2013) Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: a population-based study, 2004-2007. Thorax 68:551–564

    Article  PubMed  Google Scholar 

  38. Broggio JBN (2016) Cancer survival by stage at diagnosis for England. Office for National Statistics, Newport, UK

    Google Scholar 

  39. Bernhardt EB, Jalal SI (2016) Small Cell Lung Cancer. Cancer Treat Res 170:301–322

    Article  PubMed  Google Scholar 

  40. Blandin Knight S, Crosbie PA, Balata H, Chudziak J, Hussell T, Dive C (2017) Progress and prospects of early detection in lung cancer. Open Biol 7:170070

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Weinstein IB, Joe A (2008) Oncogene addiction. Cancer Res 68:3077–3080; discussion 3080

    Article  CAS  PubMed  Google Scholar 

  42. Robinson DR, Wu YM, Lin SF (2000) The protein tyrosine kinase family of the human genome. Oncogene 19:5548–5557

    Article  CAS  PubMed  Google Scholar 

  43. Sharma SV, Bell DW, Settleman J, Haber DA (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7:169–181

    Article  CAS  PubMed  Google Scholar 

  44. Rowinsky EK (2004) The erbB family: targets for therapeutic development against cancer and therapeutic strategies using monoclonal antibodies and tyrosine kinase inhibitors. Annu Rev Med 55:433–457

    Article  CAS  PubMed  Google Scholar 

  45. Hirsch FR, Varella-Garcia M, Bunn PA Jr, Di Maria MV, Veve R, Bremmes RM, Barón AE, Zeng C, Franklin WA (2003) Epidermal growth factor receptor in non-small-cell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol 21:3798–3807

    Article  CAS  PubMed  Google Scholar 

  46. Nicholson RI, Gee JM, Harper ME (2001) EGFR and cancer prognosis. Eur J Cancer 37(Suppl 4):S9–S15

    Article  CAS  PubMed  Google Scholar 

  47. Shigematsu H, Gazdar AF (2006) Somatic mutations of epidermal growth factor receptor signaling pathway in lung cancers. Int J Cancer 118:257–262

    Article  CAS  PubMed  Google Scholar 

  48. Gazdar AF, Shigematsu H, Herz J, Minna JD (2004) Mutations and addiction to EGFR: the Achilles ‘heal’ of lung cancers? Trends Mol Med 10:481–486

    Article  CAS  PubMed  Google Scholar 

  49. Pao W, Wang TY, Riely GJ, Miller VA, Pan Q, Ladanyi M, Zakowski MF, Heelan RT, Kris MG, Varmus HE (2005) KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2:e17

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Zhou BB, Peyton M, He B, Liu C, Girard L, Caudler E, Lo Y, Baribaud F, Mikami I, Reguart N, Yang G, Li Y, Yao W, Vaddi K, Gazdar AF, Friedman SM, Jablons DM, Newton RC, Fridman JS, Minna JD, Scherle PA (2006) Targeting ADAM-mediated ligand cleavage to inhibit HER3 and EGFR pathways in non-small cell lung cancer. Cancer Cell 10:39–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Zhang J, Iwanaga K, Choi KC, Wislez M, Raso MG, Wei W, Wistuba II, Kurie JM (2008) Intratumoral epiregulin is a marker of advanced disease in non-small cell lung cancer patients and confers invasive properties on EGFR-mutant cells. Cancer Prev Res 1:201–207

    Article  CAS  Google Scholar 

  52. Yonesaka K, Zejnullahu K, Lindeman N, Homes AJ, Jackman DM, Zhao F, Rogers AM, Johnson BE, Jänne PA (2008) Autocrine production of amphiregulin predicts sensitivity to both gefitinib and cetuximab in EGFR wild-type cancers. Clin Cancer Res 14:6963–6973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ji H, Wang Z, Perera SA, Li D, Liang MC, Zaghlul S, McNamara K, Chen L, Albert M, Sun Y, Al-Hashem R, Chirieac LR, Padera R, Bronson RT, Thomas RK, Garraway LA, Jänne PA, Johnson BE, Chin L, Wong KK (2007) Mutations in BRAF and KRAS converge on activation of the mitogen-activated protein kinase pathway in lung cancer mouse models. Cancer Res 67:4933–4939

    Article  CAS  PubMed  Google Scholar 

  54. Zhang W, Stabile LP, Keohavong P, Romkes M, Grandis JR, Traynor AM, Siegfried JM (2006) Mutation and polymorphism in the EGFR-TK domain associated with lung cancer. J Thorac Oncol 1:635–647

    PubMed  Google Scholar 

  55. Samuels Y, Diaz LA Jr, Schmidt-Kittler O, Cummins JM, Delong L, Cheong I, Rago C, Huso DL, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE (2005) Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 7:561–573

    Article  CAS  PubMed  Google Scholar 

  56. Garnis C, Lockwood WW, Vucic E, Ge Y, Girard L, Minna JD, Gazdar AF, Lam S, MacAulay C, Lam WL (2006) High resolution analysis of non-small cell lung cancer cell lines by whole genome tiling path array CGH. Int J Cancer 118:1556–1564

    Article  CAS  PubMed  Google Scholar 

  57. Meyerson M (2007) Cancer: broken genes in solid tumours. Nature 448:545–546

    Article  CAS  PubMed  Google Scholar 

  58. Olivier M, Petitjean A, Marcel V, Pétré A, Mounawar M, Plymoth A, de Fromentel CC, Hainaut P (2009) Recent advances in p53 research: an interdisciplinary perspective. Cancer Gene Ther 16:1–12

    Article  CAS  PubMed  Google Scholar 

  59. Brambilla E, Gazzeri S, Lantuejoul S, Coll JL, Moro D, Negoescu A, Brambilla C (1998) p53 mutant immunophenotype and deregulation of p53 transcription pathway (Bcl2, Bax, and Waf1) in precursor bronchial lesions of lung cancer. Clin Cancer Res 4:1609–1618

    CAS  PubMed  Google Scholar 

  60. Jeanmart M, Lantuejoul S, Fievet F, Moro D, Sturm N, Brambilla C, Brambilla E (2003) Value of immunohistochemical markers in preinvasive bronchial lesions in risk assessment of lung cancer. Clin Cancer Res 9:2195–2203

    CAS  PubMed  Google Scholar 

  61. Eymin B, Gazzeri S, Brambilla C, Brambilla E (2002) Mdm2 overexpression and p14(ARF) inactivation are two mutually exclusive events in primary human lung tumors. Oncogene 21:2750–2761

    Article  CAS  PubMed  Google Scholar 

  62. Gazzeri S, Della Valle V, Chaussade L, Brambilla C, Larsen CJ, Brambilla E (1998) The human p19ARF protein encoded by the beta transcript of the p16INK4a gene is frequently lost in small cell lung cancer. Cancer Res 58:3926–3931

    CAS  PubMed  Google Scholar 

  63. Kwak JJ, Tirumani SH, Van den Abbeele AD, Koo PJ, Jacene HA (2015) Cancer immunotherapy: imaging assessment of novel treatment response patterns and immune-related adverse events. Radiographics 35:424–437

    Article  PubMed  Google Scholar 

  64. Schuster M, Nechansky A, Kircheis R (2006) Cancer immunotherapy. Biotechnol J 1:138–147

    Article  CAS  PubMed  Google Scholar 

  65. Hu Z, Ott PA, Wu CJ (2018) Towards personalized, tumour-specific, therapeutic vaccines for cancer. Nat Rev Immunol 18:168–182

    Article  CAS  PubMed  Google Scholar 

  66. Rasmi RR, Sakthivel KM, Guruvayoorappan C (2020) NF-kappaB inhibitors in treatment and prevention of lung cancer. Biomed Pharmacother 130:110569

    Article  CAS  PubMed  Google Scholar 

  67. Keir ME, Butte MJ, Freeman GJ, Sharpe AH (2008) PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26:677–704

    Article  CAS  PubMed  Google Scholar 

  68. Topalian SL, Drake CG, Pardoll DM (2012a) Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol 24:207–212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8:793–800

    Article  CAS  PubMed  Google Scholar 

  70. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M (2012b) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Rajan A, Gulley JL (2014) Nivolumab (anti-PD-1, BMS-936558, ONO-4538) in patients with advanced non-small cell lung cancer. Transl Lung Cancer Res 3:403–405

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Topalian SL, Sznol M, Brahmer JR, McDermott DF, Smith DC, Gettinger SN, Taube JM, Drake CG, Pardoll DM, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Antonia SJ, Spigel DR, Lawrence DP, Kollia G, Gupta AK, Wigginton JM, Hodi FS (2013) Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with advanced solid tumors: survival and long-term safety in a phase I trial. J Clin Oncol 31:3002–3002

    Article  Google Scholar 

  73. Grosso J, Horak CE, Inzunza D, Cardona DM, Simon JS, Gupta AK, Sankar V, Park J-S, Kollia G, Taube JM, Anders R, Jure-Kunkel M, Jim Novotny J, Taylor CR, Zhang X, Phillips T, Simmons P, Cogswell J (2013) Association of tumor PD-L1 expression and immune biomarkers with clinical activity in patients (pts) with advanced solid tumors treated with nivolumab (anti-PD-1; BMS-936558; ONO-4538). J Clin Oncol 31:3016–3016

    Article  Google Scholar 

  74. Spigel DR, Gettinger SN, Horn L, Herbst RS, Gandhi L, Gordon MS, Cruz C, Conkling P, Cassier PA, Antonia SJ, Burris HA, Fine GD, Mokatrin A, Kowanetz M, Shen X, Chen DS, Soria J-C (2013) Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). J Clin Oncol 31:8008–8008

    Article  Google Scholar 

  75. Metro G (2018) EGFR targeted therapy for lung cancer: are we almost there? Transl Lung Cancer Res 7:S142–S145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Ray MR, Jablons D, He B (2010) Lung cancer therapeutics that target signaling pathways: an update. Expert Rev Respir Med 4:631–645

    Article  PubMed  PubMed Central  Google Scholar 

  77. Heist RS, Christiani D (2009) EGFR-targeted therapies in lung cancer: predictors of response and toxicity. Pharmacogenomics 10:59–68

    Article  CAS  PubMed  Google Scholar 

  78. Fujiwara A, Yoshida M, Fujimoto H, Nakahara H, Ito K, Nishihama K, Yasuma T, Hataji O, Taguchi O, D’Alessandro-Gabazza CN, Gabazza EC, Kobayashi T (2018) A retrospective comparison of the clinical efficacy of gefitinib, erlotinib, and afatinib in Japanese patients with non-small cell lung cancer. Oncol Res 26:1031–1036

    Article  PubMed  PubMed Central  Google Scholar 

  79. Tu CY, Chen CM, Liao WC, Wu BR, Chen CY, Chen WC, Hsia TC, Cheng WC, Chen CH (2018) Comparison of the effects of the three major tyrosine kinase inhibitors as first-line therapy for non-small-cell lung cancer harboring epidermal growth factor receptor mutations. Oncotarget 9:24237–24247

    Article  PubMed  PubMed Central  Google Scholar 

  80. Hu Z, Li M, Chen Z, Zhan C, Lin Z, Wang Q (2019) Advances in clinical trials of targeted therapy and immunotherapy of lung cancer in 2018. Transl Lung Cancer Res 8:1091–1106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Fresno Vara JA, Casado E, de Castro J, Cejas P, Belda-Iniesta C, Gonzalez-Baron M (2004) PI3K/Akt signalling pathway and cancer. Cancer Treat Rev 30:193–204

    Article  PubMed  CAS  Google Scholar 

  82. Andrew S (1999) PIK3CA: determining its role in cellular proliferation and ovarian cancer. Clin Genet 56:190–191

    Article  CAS  PubMed  Google Scholar 

  83. Lu Y, Wang H, Mills GB (2003) Targeting PI3K-AKT pathway for cancer therapy. Rev Clin Exp Hematol 7:205–228

    CAS  PubMed  Google Scholar 

  84. Osaki M, Oshimura M, Ito H (2004) PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 9:667–676

    Article  CAS  PubMed  Google Scholar 

  85. Kandasamy K, Srivastava RK (2002) Role of the phosphatidylinositol 3′-kinase/PTEN/Akt kinase pathway in tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in non-small cell lung cancer cells. Cancer Res 62:4929–4937

    CAS  PubMed  Google Scholar 

  86. Brahmer JR (2013) Harnessing the immune system for the treatment of non-small-cell lung cancer. J Clin Oncol 31:1021–1028

    Article  CAS  PubMed  Google Scholar 

  87. Holt GE, Podack ER, Raez LE (2011) Immunotherapy as a strategy for the treatment of non-small-cell lung cancer. Therapy 8:43–54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Gure AO, Chua R, Williamson B, Gonen M, Ferrera CA, Gnjatic S, Ritter G, Simpson AJG, Chen Y-T, Old LJ, Altorki NK (2005) Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer. Clin Cancer Res 11:8055–8062

    Article  CAS  PubMed  Google Scholar 

  89. Sienel W, Varwerk C, Linder A, Kaiser D, Teschner M, Delire M, Stamatis G, Passlick B (2004) Melanoma associated antigen (MAGE)-A3 expression in Stages I and II non-small cell lung cancer: results of a multi-center study. Eur J Cardiothorac Surg 25:131–134

    Article  CAS  PubMed  Google Scholar 

  90. Vansteenkiste J, Zielinski M, Linder A, Dahabreh J, Gonzalez EE, Malinowski W, Lopez-Brea M, Vanakesa T, Jassem J, Kalofonos H, Perdeus J, Bonnet R, Basko J, Janilionis R, Passlick B, Treasure T, Gillet M, Lehmann FF, Brichard VG (2013) Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase II randomized study results. J Clin Oncol 31:2396–2403

    Article  CAS  PubMed  Google Scholar 

  91. Tyagi P, Mirakhur B (2009) MAGRIT: the largest-ever phase III lung cancer trial aims to establish a novel tumor-specific approach to therapy. Clin Lung Cancer 10:371–374

    Article  PubMed  Google Scholar 

  92. Quoix E, Lena H, Losonczy G, Forget F, Chouaid C, Papai Z, Gervais R, Ottensmeier C, Szczesna A, Kazarnowicz A, Beck JT, Westeel V, Felip E, Debieuvre D, Madroszyk A, Adam J, Lacoste G, Tavernaro A, Bastien B, Halluard C, Palanché T, Limacher JM (2016) TG4010 immunotherapy and first-line chemotherapy for advanced non-small-cell lung cancer (TIME): results from the phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial. Lancet Oncol 17:212–223

    Article  CAS  PubMed  Google Scholar 

  93. Xia W, Wang J, Xu Y, Jiang F, Xu L (2014) L-BLP25 as a peptide vaccine therapy in non-small cell lung cancer: a review. J Thorac Dis 6:1513–1520

    PubMed  PubMed Central  Google Scholar 

  94. Hirasawa Y, Kohno N, Yokoyama A, Kondo K, Hiwada K, Miyake M (2000) Natural autoantibody to MUC1 is a prognostic indicator for non-small cell lung cancer. Am J Respir Crit Care Med 161:589–594

    Article  CAS  PubMed  Google Scholar 

  95. Butts C, Socinski MA, Mitchell PL, Thatcher N, Havel L, Krzakowski M, Nawrocki S, Ciuleanu TE, Bosquée L, Trigo JM, Spira A, Tremblay L, Nyman J, Ramlau R, Wickart-Johansson G, Ellis P, Gladkov O, Pereira JR, Eberhardt WE, Helwig C, Schröder A, Shepherd FA (2014) Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial. Lancet Oncol 15:59–68

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Lab Technology, University Institute of Applied Health Sciences, Chandigarh University, Mohali, Punjab, India

    Gurjit Kaur Bhatti

  2. Department of Biotechnology, Sri Guru Gobind Singh College, Chandigarh, India

    Paras Pahwa & Anshika Gupta

  3. Department of Pharmacology, Central University of Punjab, Bathinda, Punjab, India

    Umashanker Navik

  4. Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, Punjab, India

    Jasvinder Singh Bhatti

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  1. Gurjit Kaur Bhatti
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  2. Paras Pahwa
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  3. Anshika Gupta
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  4. Umashanker Navik
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  5. Jasvinder Singh Bhatti
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Correspondence to Jasvinder Singh Bhatti .

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Editors and Affiliations

  1. Graduate School of Health, Discipline of Pharmacy, University of Technology Sydney, Sydney, NSW, Australia

    Kamal Dua

  2. Drug Development and Innovation Centre, University of Alberta, Edmonton, AB, Canada

    Raimar Löbenberg

  3. Haematology and Hemotherapy Center, State University of Campinas, Campinas, São Paulo, Brazil

    Ângela Cristina Malheiros Luzo

  4. Graduate School of Health, Discipline of Pharmacy, University of Technology Sydney, Sydney, NSW, Australia

    Shakti Shukla

  5. School of Pharmaceutical Sciences & Division of Research & Development, Lovely Professional University, Phagwara, Punjab, India

    Saurabh Satija

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Bhatti, G.K., Pahwa, P., Gupta, A., Navik, U., Bhatti, J.S. (2021). Therapeutic Strategies Targeting Signaling Pathways in Lung Cancer. In: Dua, K., Löbenberg, R., Malheiros Luzo, Â.C., Shukla, S., Satija, S. (eds) Targeting Cellular Signalling Pathways in Lung Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-33-6827-9_9

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