Skip to main content
SpringerLink
Log in

Target Therapy in Lung Cancer

  • Chapter
  • First Online:
Lung Cancer and Personalized Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 893))

Abstract

Lung cancer is an extremely heterogeneous disease, with well over 50 different histological variants recognized under the fourth revision of the World Health Organization (WHO) typing system [1]. Because these variants have differing genetic and biological properties correct classification of lung cancer is necessary to assure that lung cancer patients receive optimum management. Due to the recent understanding that histologic typing and EGFR mutation status are important for target the therapy in lung adenocarcinoma patients [2] there was a great need for a new classification that addresses diagnostic issues and strategic management to allow for molecular testing in small biopsy and cytology specimens. For this reason and in order to address advances in lung cancer treatment an international multidisciplinary classification was proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS) [3], further increasing the histological heterogeneity and improving the existing WHO-classification. Is now the beginning of personalized therapy era that is ideally finalized to treat each individual case of lung cancer in different way.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (eds) (2004) World Health Organization classification of tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. IARC Press, Lyon

    Google Scholar 

  2. Antonicelli A, Cafarotti S, Indini A, Galli A et al (2013) EGFR-targeted therapy for non-small cell lung cancer: focus on EGFR oncogenic mutation. Int J Med Sci 10(3):320–330

    Article  PubMed Central  PubMed  Google Scholar 

  3. Travis WD et al (2011) IASLC/ATS/ERS international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6(2):244–285

    Article  PubMed Central  PubMed  Google Scholar 

  4. Cheng L, Zhang S, Alexander R et al (2011) The landscape of EGFR pathways and personalized management of non-small-cell lung cancer. Future Oncol 7:519–541

    Article  CAS  PubMed  Google Scholar 

  5. Normanno N, De Luca A, Bianco C et al (2006) Epidermal growth factor receptor (EGFR) signaling in cancer. Gene 366:2–16

    Article  CAS  PubMed  Google Scholar 

  6. Hynes NE, Lane HA (2005) ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 5:341–354

    Article  CAS  PubMed  Google Scholar 

  7. Hirsch FR, Varella-Garcia M, Capuzzo F (2009) Predictive value of EGFR and HER2 overexpression in advanced non-small-cell lung cancer. Oncogene 28:S32–S37

    Article  CAS  PubMed  Google Scholar 

  8. Quesnelle KM, Boehm AL, Grandis JR (2007) STAT-mediated EGFR signaling in cancer. J Cell Biochem 102(2):311–319

    Article  CAS  PubMed  Google Scholar 

  9. Wang X, Zhang S, MacLennan GT et al (2008) Epidermal growth factor receptor protein expression and gene amplification in the chemorefractory metastatic embryonal carcinoma. Mod Pathol 22:7–12

    Article  PubMed  Google Scholar 

  10. Wang X, Zhang S, MacLennan GT et al (2007) Epidermal growth factor receptor protein expression and gene amplification in small cell carcinoma of the urinary bladder. Clin Cancer Res 13:953–957

    Article  CAS  PubMed  Google Scholar 

  11. Herbst RS, Heymach JV, Lippman SM (2008) Lung cancer. N Engl J Med 359:1367–1380

    Article  CAS  PubMed  Google Scholar 

  12. Costa DB, Halmos B, Kumar A et al (2007) BIM mediates EGFR tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic EGFR mutations. PLoS Med 4:1669–1679

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  14. Sequist LV, Bell DW, Lynch TJ et al (2007) Molecular predictor of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. J Clin Oncol 25:587–595

    Article  CAS  PubMed  Google Scholar 

  15. Ladanyi M, Pao W (2008) Lung adenocarcinoma: guiding EGFR-targeted therapy and beyond. Mod Pathol 21(Suppl 2):S16–S22

    Article  CAS  PubMed  Google Scholar 

  16. Shigematsu H, Lin L, Takahashi T et al (2005) Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancer. J Natl Cancer Inst 97:339–346

    Article  CAS  PubMed  Google Scholar 

  17. Pao W, Girard N (2011) New driver mutations in non-small-cell lung cancer. Lancet Oncol 12:175–180

    Article  CAS  PubMed  Google Scholar 

  18. Yamamoto H, Toyooka S, Mitsudomi T (2009) Impact of EGFR mutation analysis in non-small-cell lung cancer. Lung Cancer 63:315–321

    Article  PubMed  Google Scholar 

  19. Eberhard DA, Johnson BE, Amler LC et al (2005) Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol 23:5900–5909

    Article  CAS  PubMed  Google Scholar 

  20. Schrump DS, Altorki NK, Henschke CL et al (2005) Non-small cell lung cancer. In: DeVita VT (ed) Cancer: principles and practices of oncology. Lippincott Williams & Wilkins, Philadelphia, pp 753–810

    Google Scholar 

  21. Azzoli CG, Baker S Jr, Temin S et al (2009) American society of clinical oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol 27:6251–6266

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Fossella F, Pereira JR, von Pawel J et al (2003) Randomized, multinational phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol 21:3016–3022

    Article  CAS  PubMed  Google Scholar 

  23. Sandler A, Gray R, Perry MC et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550

    Article  CAS  PubMed  Google Scholar 

  24. Shepherd FA, Dancey J, Ramlau R et al (2000) Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 18:2095–2103

    Article  CAS  PubMed  Google Scholar 

  25. Hanna N, Shepherd FA, Fossella FV et al (2004) Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 22:1589–1597

    Article  CAS  PubMed  Google Scholar 

  26. Shepherd FA, Rodrigues PJ, Ciuleanu T et al (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353:123–132

    Article  CAS  PubMed  Google Scholar 

  27. Lynch TJ, Bell DW, Sordella R et al (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350:2129–2139

    Article  CAS  PubMed  Google Scholar 

  28. Paez JG, Janne PA, Lee JC et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500

    Article  CAS  PubMed  Google Scholar 

  29. Fujita S, Katakami N, Masago K et al (2012) Customized chemotherapy based on epidermal growth factor receptor mutation status for elderly patients with advanced non-small-cell lung cancer: a phase II trial. BMC Cancer 12:185

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Mok TS, Wu YL, Thongprasert S et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947–957

    Article  CAS  PubMed  Google Scholar 

  31. Maemondo M, Inoue A, Kobayashi K et al (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388

    Article  CAS  PubMed  Google Scholar 

  32. Nguyen KS, Kobayashi S, Costa DB (2009) Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway. Clin Lung Cancer 10:281–289

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Jackman D, Pao W, Riely GJ et al (2010) Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol 28:357–360

    Article  CAS  PubMed  Google Scholar 

  34. Suda K, Onozato R, Yatabe Y et al (2009) EGFR T790M mutation: a double role in lung cancer survival? J Thorac Oncol 4:1–4

    Article  PubMed  Google Scholar 

  35. Pao W, Miller VA, Politi KA et al (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2:e73, Int J Med Sci (2013) Vol. 10 http://www.medsci.org 329

    Article  PubMed Central  PubMed  Google Scholar 

  36. Yun CH, Mengwasser KE, Toms AV et al (2008) The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci USA 105:2070–2075

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Chen HJ, Mok TS, Chen ZH et al (2009) Clinicopathologic and molecular features of epidermal growth factor receptor T790M mutation and c-MET amplification in tyrosine kinase inhibitor-resistant Chinese non small cell lung cancer. Pathol Oncol Res 15:651–658

    Article  CAS  PubMed  Google Scholar 

  38. Viloria-Petit A, Crombet T, Jothy S et al (2001) Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis. Cancer Res 61:5090–5101

    CAS  PubMed  Google Scholar 

  39. Guix M, Faber AC, Wang SE et al (2008) Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. J Clin Invest 118:2609–2619

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Okudela K, Suzuki M, Kageyama S et al (2007) PIK3CA mutation and amplification in human lung cancer. Pathol Int 57:664–671

    Article  CAS  PubMed  Google Scholar 

  41. Yamamoto H, Shigematsu H, Nomura M et al (2008) PIK3CA mutations and copy number gains in human lung cancers. Cancer Res 68:6913–6921

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Sequist LV, Waltman BA, Dias-Santagata D et al (2011) Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 3, 75ra26

    Article  PubMed Central  PubMed  Google Scholar 

  43. Sequist LV, Besse B, Lynch TJ et al (2010) Neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor: results of phase II trial in patients with advanced non small-cell lung cancer. J Clin Oncol 28:3076–3083

    Article  CAS  PubMed  Google Scholar 

  44. Jakobsen JN, Sorensen JB (2012) Intratumor heterogeneity and chemotherapy-induced changes in EGFR status in non-small cell lung cancer. Cancer Chemother Pharmacol 69(2):289–299

    Article  CAS  PubMed  Google Scholar 

  45. Rosell R, Moran T, Queralt C et al (2009) Screening for epidermal growth factor receptor (EGFR) mutations in lung cancer. N Engl J Med 361:958–966

    Article  CAS  PubMed  Google Scholar 

  46. Thatcher N, Chang A, Parikh P et al (2005) Gefitinib plus best supportive care in previously treated patients with refractory advanced nonsmall-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 366:1527–1537

    Article  CAS  PubMed  Google Scholar 

  47. Bai H, Wang Z, Chen K, Zhao J, Lee JJ, Wang S, Zhou Q, Zhuo M, Mao L, An T, Duan J, Yang L, Wu M, Liang Z, Wang Y, Kang X, Wang J (2012) Influence of chemotherapy on EGFR mutation status among patients with non-small-cell lung cancer. J Clin Oncol 30(25):3077–3083

    Article  PubMed Central  PubMed  Google Scholar 

  48. Warth A, Macher-Goeppinger S, Muley T, Thomas M, Hoffmann H, Schnabel PA, Penzel R, Schirmacher P, Aulmann S (2012) Clonality of multifocal non-small cell lung cancer: implications for staging and therapy. Eur Respir J 39:1437–1442

    Article  CAS  PubMed  Google Scholar 

  49. Girard N, Deshpande C, Azzoli CG, Rusch VW, Travis WD, Ladanyi M, Pao W (2010) Use of epidermal growth factor receptor/Kirsten rat sarcoma 2 viral oncogene homolog mutation testing to define clonal relationships among multiple lung adenocarcinomas: comparison with clinical guidelines. Chest 137(1):46–52

    Article  CAS  PubMed  Google Scholar 

  50. Chung JH, Choe G, Jheon S, Sung SW, Kim TJ, Lee KW, Lee JH, Lee CT (2009) Epidermal growth factor receptor mutation and pathologic-radiologic correlation between multiple lung nodules with ground-glass opacity differentiates multicentric origin from intrapulmonary spread. J Thorac Oncol 4(12):1490–1495

    Article  PubMed  Google Scholar 

  51. Lococo F, Cesario A, Leuzzi G, Apolone G (2014) Second primary non-small-cell lung cancer: implications of the new adenocarcinoma classification in the challenging decision of the best surgical strategy. Eur J Cardiothorac Surg 45:1115–1116

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unit of Thoracic Surgery, EOC-ORBV, Bellinzona, Switzerland

    Stefano Cafarotti

  2. Unit of Thoracic Surgery, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy

    Filippo Lococo

  3. Unit of Oncology, IOSI, Bellinzona, Switzerland

    Patrizia Froesh

  4. Unit of Oncology, Clinica Luganese Moncucco, Lugano, Switzerland

    Francesco Zappa

  5. Unit of Thoracic Surgery, Chefarzt der neuen Klinik für Thoraxchirurgie am Kantonsspital, St. Gallen, Switzerland

    Dutly Andrè

Authors
  1. Stefano Cafarotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Filippo Lococo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patrizia Froesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francesco Zappa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dutly Andrè
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stefano Cafarotti .

Editor information

Editors and Affiliations

  1. Wayne State University, Karmanos Cancer Institute, Detroit, Michigan, USA

    Aamir Ahmad

  2. Wayne State University, Karmanos Cancer Institute, Detroit, Michigan, USA

    Shirish Gadgeel

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Cafarotti, S., Lococo, F., Froesh, P., Zappa, F., Andrè, D. (2016). Target Therapy in Lung Cancer. In: Ahmad, A., Gadgeel, S. (eds) Lung Cancer and Personalized Medicine. Advances in Experimental Medicine and Biology, vol 893. Springer, Cham. https://doi.org/10.1007/978-3-319-24223-1_6

Download citation

Publish with us

Policies and ethics

Search

Navigation