Skip to main content
SpringerLink
Log in

Biomarkers in bronchopulmonary cancer

  • Educational Series
  • Current Technology in Cancer Research and Treatment
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Non-small-cell lung cancer (NSCLC) ranks among the neoplasms with the worst prognoses and the highest mortality rates. Several factors, mainly clinical, are known that provide a predictive value on the course of the disease. In the era in which we live, the molecular basis of cancer is studied in depth and several molecular markers have been described that could play a prognostic role or that could predict the probability of responding to the different treatments used. Moreover, some mechanisms have been proposed that could explain primary or acquired resistance to treatment with chemotherapy and to targeted therapies. Knowing all these pathways is very important, as it allows the development of selective therapeutic strategies that minimise toxicity and optimise treatment effectiveness. However, the data obtained yield results that are at times contradictory, prospective studies with biomarkers thus being necessary so that their role can be established with the necessary evidence.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mountain CF (1995) New prognostic factors in lung cancer. Biologic prophets of cancer cell aggression. Chest 108:246

    Article  CAS  PubMed  Google Scholar 

  2. Salgia R, Skarin AT (1998) Molecular abnormalities in lung cancer. J Clin Oncol 16:1207

    CAS  PubMed  Google Scholar 

  3. Rosell R, Felip E, Garcia-Campelo R, Balana C (2004) The biology of non-small-cell lung cancer: identifying new targets for rational therapy. Lung Cancer 46:135

    Article  CAS  PubMed  Google Scholar 

  4. Sawyers CL (2008) The cancer biomarker problem. Nature 452:548–552

    Article  CAS  PubMed  Google Scholar 

  5. Hibi K, Takahashi T, Yamakawa K et al (1992) Three distinct regions involved in 3p deletion in human lung cancer. Oncogene 7:445

    CAS  PubMed  Google Scholar 

  6. Hirao T, Nelson HH, Ashok TD et al (2001) Tobacco smoke-induced DNA damage and an early age of smoking initiation induce chromosome loss at 3p21 in lung cancer. Cancer Res 61:612

    CAS  PubMed  Google Scholar 

  7. Sozzi G, Veronese ML, Negrini M et al (1996) The FHIT gene 3p14.2 is abnormal in lung cancer. Cell 85:17

    Article  CAS  PubMed  Google Scholar 

  8. Maruyama R, Sugio K, Yoshino I et al (2004) Hypermethylation of FHIT as a prognostic marker in non-small cell lung carcinoma. Cancer 100:1472

    Article  CAS  PubMed  Google Scholar 

  9. Hahn WC (2003) Role of telomeres and telomerase in the pathogenesis of human cancer. J Clin Oncol 21:2034

    Article  CAS  PubMed  Google Scholar 

  10. Sánchez-Céspedes M (2009) Lung cancer biology: a genetic and genomic perspective. Clin Transl Oncol 11:263–269

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  12. Chen HY, Yu SL, Chen CH et al (2007) A fivegene signature and clinical outcome in non-smallcell lung cancer. N Engl J Med 356:11–20

    Article  CAS  PubMed  Google Scholar 

  13. Potti A, Mukherjee S, Petersen R et al (2006) A genomic strategy to refine prognosis in earlystage non-small-cell lung cancer. N Engl J Med 355:570–580

    Article  CAS  PubMed  Google Scholar 

  14. Sun Z, Wigle DA, Yang P (2008) Non-overlapping and non-cell-type-specific gene expression signatures predict lung cancer survival. J Clin Oncol 26:877–883

    Article  PubMed  Google Scholar 

  15. Garrido P, Fernández Abad M, Olmedo ME (2009) Molecular selection treatment on lung cancer. Cancer and Chemotherapy Rev 4:44–51.

    Google Scholar 

  16. Olaussen KA, Dunant A, Fouret P et al (2006) DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 355:983–991

    Article  CAS  PubMed  Google Scholar 

  17. Cobo M, Isla D, Massuti B et al (2007) Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol 25:2747–2754

    Article  CAS  PubMed  Google Scholar 

  18. West H, Lilenbaum R, Harpole D et al (2009) Molecular analysis-based treatment strategies for the management of non-small cell lung cancer. J Thorac Oncol 4:S1029–S1039

    Article  PubMed  Google Scholar 

  19. Bepler G, Kusmartseva I, Sharma S et al (2006) RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol 24:4731–4737

    Article  CAS  PubMed  Google Scholar 

  20. Rosell R, Danenberg KD, Alberola V et al (2004) Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients. Clin Cancer Res 10:1318–1325

    Article  CAS  PubMed  Google Scholar 

  21. Bepler G, Li X, Schell MJ et al (2008) Predictive value of RRM1 and ERCC1 protein levels in a prospective community-based trial of gemcitabine/carboplatin (GC) vs gemcitabine (G) alone. J Clin Oncol 2008 ASCO Annual Meeting Proc Part I; 26 (abstr 8033)

  22. Simon G, Sharma A, Li X et al (2007) Feasibility and efficacy of molecular analysis-directed individualized therapy in advanced non-small-cell lung cancer. J Clin Oncol 25:2741–2746

    Article  CAS  PubMed  Google Scholar 

  23. Ozasa H, Oguri T, Uemura T et al (2009) Significance of thymidylate synthase for resistance to pemetrexed in lung cancer. Cancer Sci 101:161–166

    Article  CAS  PubMed  Google Scholar 

  24. Scagliotti GV, Parikh P, Felip E et al (2008) Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapynaïve patients with advanced-stage NSCLC. J Clin Oncol 26:3543–3551

    Article  CAS  PubMed  Google Scholar 

  25. Taron M, Rosell R, Felip E et al (2004) BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer. Hum Mol Genet 13:2443–2449

    Article  CAS  PubMed  Google Scholar 

  26. Fasano J, Muggia F (2009) Breast cancer arising in a BRCA-mutated background: therapeutic implications from an animal model and drug development. Ann Oncol 20:609–614

    Article  CAS  PubMed  Google Scholar 

  27. Hsu JY, Wakelee H (2009) Monoclonal antibodies targeting vascular endothelial growth factor: current status and future challenges in cancer therapy. BioDrugs 23:289–304

    Article  CAS  PubMed  Google Scholar 

  28. Shepherd FA, Rodríguez-Pereira J, Ciuleanu T et al (2005) Erlotinib in previously treated nonsmall-cell lung cancer. N Engl J Med 353:123–132

    Article  CAS  PubMed  Google Scholar 

  29. Thatcher N, Chang A, Parikh P et al (2005) Gefitinib plus best supportive care in previously treated patients with refractory advanced non small-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 

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

    Article  CAS  PubMed  Google Scholar 

  31. 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 

  32. Pao W, Miller V, Zakowski M et al (2004) EGF receptor gene mutations are common in lung cancers from “never smokers“ and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 101:13306–13311

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  34. Uramoto H, Mitsudomi T (2007) Which biomarker predicts benefit from EGFR-TKI treatment for patients with lung cancer? Br J Cancer 96:857–863

    Article  CAS  PubMed  Google Scholar 

  35. Cortes-Funes H, Gómez C, Rosell R et al (2005) Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small cell lung cancer patients. Ann Oncol 16:1081–1086

    Article  CAS  PubMed  Google Scholar 

  36. Paz-Ares L, Sanchez JM, Garcia-Velasco A et al (2006) A prospective phase II trial of erlotinib in advanced non-small-cell lung cancer (NSCLC) patients (p) with mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR). J Clin Oncol 24[Suppl 18S]:7020a

    Google Scholar 

  37. Mok T (2008) Phase III, randomised, open-label, first-line study of gefitinib vs carboplatin/paclitaxel in clinically selected patients with advanced nonsmall-cell lung cancer. Abstract 33rd European Society of Medical Oncology Congress; September 12–16; Stockholm, Sweden. Abstract LBA2

  38. Herbst RS, Prager D, Hermann R et al (2005) TRIBUTE: a phase II trail of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 23:5892–5899

    Article  CAS  PubMed  Google Scholar 

  39. Giaccone G, Herbst RS, Manegold C et al (2004) Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial — INTACT 1. J Clin Oncol 22:777–784

    Article  CAS  PubMed  Google Scholar 

  40. Herbst RS, Giaccone G, Schiller JH et al (2004) Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial — INTACT 2. J Clin Oncol 22:785–794

    Article  CAS  PubMed  Google Scholar 

  41. Salomon DS, Brandt R, Ciardiello F et al (1995) Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 19:183–232

    Article  CAS  PubMed  Google Scholar 

  42. Ohsaki Y, Tanno S, Fujita Y et al (2000) Epidermal growth factor receptor expression correlates with poor prognosis in non-small cell lung cancer patients with p53 overexpression. Oncol Rep 7:603–607

    CAS  PubMed  Google Scholar 

  43. Hirsch FR, Varella-Garcia M, Cappuzzo F et al (2007) Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib. Ann Oncol 18:752–760

    Article  CAS  PubMed  Google Scholar 

  44. Douillard JY, Kim ES, Hirsch V et al (2007) Phase III randomized, open-label, parallel-group study of oral gefitinib (IRESSA) versus intravenous docetaxel in patients in patients with locally advanced or metastasic NSCLC who have previously received platinum-based chemotherapy (INTEREST). Eur J Cancer 5:2

    Google Scholar 

  45. Cappuzzo F, Hirsch FR, Rossi E et al (2005) Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst 97:643–655

    CAS  PubMed  Google Scholar 

  46. Hirsch FR, Varella-Garcia M, McCoy J et al (2005) Increased epidermal growth factor receptor gene copy number detected by fluorescence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: a Southwest Oncology Group Study. J Clin Oncol 23:6838–6845

    Article  CAS  PubMed  Google Scholar 

  47. Takano T, Ohe Y, Sakamoto H et al (2005) Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer. J Clin Oncol 23:6829–6837

    Article  CAS  PubMed  Google Scholar 

  48. Marijon H, Bouyon A, Vignot S, Besse B (2009) Prognostic and predictive factors in lung cancer. Bull Cancer 96:391–404

    CAS  PubMed  Google Scholar 

  49. Herbst RS, Heymach JV, Lippman SM (2008) Molecular origins of cancer. N Engl J Med 359: 1367–1380

    Article  CAS  PubMed  Google Scholar 

  50. Horn L, Pao W (2009) EML4-ALK: honing in on a new target in non-small-cell lung cancer. J Clin Oncol 26:4232–4235

    Article  CAS  Google Scholar 

  51. Jackman DM, Miller VA, Cioffredi LA et al (2009) Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials. Clin Cancer Res 15:5267–5273

    Article  CAS  PubMed  Google Scholar 

  52. Linardou H, Dahabreh IJ, Kanaloupiti D et al (2008) Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol 9:962–972

    Article  CAS  PubMed  Google Scholar 

  53. Brugger W, Triller N, Blasinska-Morawiec S et al (2009) Biomarker analyses from the phase III placebo-controlled SATURN study of maintenance erlotinib following fisrt-line chemotherapy for advanced NSCLC. J Clin Oncol 27[15s]:abstr 8020

  54. O’Byrne KJ, Bondarenko I, Barrios C et al (2009) Molecular and clinical predictors of outcome for cetuximab in non-small cell lung cancer (NSCLC): data from the FLEX study. J Clin Oncol 27[15s]:abstr 8007

  55. Marchetti A, Milella M, Felicioni L et al (2009) Clinical implications of KRAS mutations in lung cancer patients treated with tyrosine kinase inhibitors. An important role for mutations in minor clones. Neoplasia 11:1084–1092

    CAS  PubMed  Google Scholar 

  56. Sartori G, Cavazza A, Sgambato A et al (2009) EGFR and K-ras mutations along the spectrum of pulmonary epithelial tumors of the lung and elaboration of a combined clinicopathologic and molecular scoring system to predict clinical responsiveness to EGFR inhibitors. Am J Clin Pathol 131:478–489

    Article  CAS  PubMed  Google Scholar 

  57. Garassino MC, Borgonovo K, Rossi A et al (2009) Biological and clinical features in predicting efficacy of epidermal growth factor receptor tyrosine kinase inhibitors: a systematic review and metaanalysis. Anticancer Res 29:2691–2701

    CAS  PubMed  Google Scholar 

  58. Zhu CQ, da Cunha Santos G, Ding K et al (2008) Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 26:4268–4275

    Article  CAS  PubMed  Google Scholar 

  59. Kim ES, Hirsh V, Mok T et al (2008) Gefitinib versus docetaxel in previously treated non-smallcell lung cancer (INTEREST): a randomised phase III trial. Lancet 372:1809–1818

    Article  CAS  PubMed  Google Scholar 

  60. Kosaka T, Yatabe Y, Endoh H et al (2006) Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib. Clin Cancer Res 12:5764–5769

    Article  CAS  PubMed  Google Scholar 

  61. Shaw AT, Yeap BY, Mino-Kenudson M et al (2009) Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK. J Clin Oncol 27:4247–4253

    Article  CAS  PubMed  Google Scholar 

  62. Balak MN, Gong Y, Riely GJ (2006) Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res 12:6494–6501

    Article  CAS  PubMed  Google Scholar 

  63. Riely GJ (2008) Second-generation epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. J Thorac Oncol 3[Suppl 2]:S146–S149

    Article  PubMed  Google Scholar 

  64. Kosaka T, Yatabe Y, Onozato R et al (2009) Prognostic implication of EGFR, KRAS, and TP53 gene mutations in a large cohort of Japanese patients with surgically treated lung adenocarcinoma. J Thorac Oncol 4:22–29

    PubMed  Google Scholar 

  65. 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 EGFR kinase domain. PLOS Med 2:e73:0225–0232

    Article  PubMed  CAS  Google Scholar 

  66. Onitsuka T, Uramoto H, Nose N et al (2009) Acquired resistance to gefitinib: the contribution of mechanisms other than the T790M, MET, and HGF status. Lung Cancer [Epub ahead of print]

  67. Okabe T, Okamoto I, Tsukioka S et al (2009) Addition of S-1 to the epidermal growth factor receptor inhibitor gefitinib overcomes resistance in non-small cell lung cancer lines with MET amplification. Clin Cancer Res 15:907–913

    Article  CAS  PubMed  Google Scholar 

  68. Rossi A, Maione P, Ferrara ML et al (2009) Angiogenesis inhibitors and vascular disrupting agents in non-small cell lung cancer. Curr Med Chem 16:3919–3930

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Servicio de Oncología Médica, Hospital Universitario La Fe, Avda. Campanar, 21, ES-46009, Valencia, Spain

    María Martín Ureste & Joaquín Montalar Salcedo

  2. Hospital Lluis Alcanys Xátiva, Valencia, Spain

    Regina Gironés Sarrió

Authors
  1. María Martín Ureste
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Regina Gironés Sarrió
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joaquín Montalar Salcedo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joaquín Montalar Salcedo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martín Ureste, M., Gironés Sarrió, R. & Montalar Salcedo, J. Biomarkers in bronchopulmonary cancer. Clin Transl Oncol 12, 92–99 (2010). https://doi.org/10.1007/S12094-010-0475-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/S12094-010-0475-y

Keywords

Search

Navigation