Skip to main content
SpringerLink
Log in

Prädiktive Biomarker tumorrelevanter Signalwege in der molekularen Pathologie

Predictive biomarkers for tumor-relevant signaling pathways in molecular pathology

  • CME Zertifizierte Fortbildung
  • Published:
Der Pathologe Aims and scope Submit manuscript

Zusammenfassung

Die personalisierte Medizin erfährt in der Onkologie eine rasante Weiterentwicklung gerichteter Therapieansätze. Tumorbehandlungen werden mehr und mehr für Patienten je nach entscheidenden molekularen Alterationen individuell maßgeschneidert, um therapeutische Effekte zu maximieren und das Gesamtüberleben zu verbessern. Der Pathologe hat mittlerweile eine zentrale Rolle bei der Untersuchung und Identifizierung molekularer Biomarker, die für eine bessere prognostische Beurteilung und Abschätzung des Therapieerfolgs im Hinblick auf spezifische zielgerichtete Therapieansätze benötigt werden.

Abstract

In the era of personalized medicine, targeted cancer treatments aim to improve therapy and overall survival. Specific therapies are individually customized for patients based on molecular alterations of the neoplastic cells. The pathologist has a central role in the identification and characterization of a variety of molecular markers that can be used to better predict outcome and assess therapeutic success of specific targeted approaches.

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

Abb. 1
Abb. 2
Abb. 3

Literatur

  1. Mccubrey JA, Steelman LS, Chappell WH et al (2007) Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 1773:1263–1284

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Fernandez-Medarde A, Santos E (2011) Ras in cancer and developmental diseases. Genes Cancer 2:344–358

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Pratilas CA, Solit DB (2010) Targeting the mitogen-activated protein kinase pathway: physiological feedback and drug response. Clin Cancer Res 16:3329–3334

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Ardini E, Magnaghi P, Orsini P et al (2010) Anaplastic Lymphoma Kinase: role in specific tumours, and development of small molecule inhibitors for cancer therapy. Cancer Lett 299:81–94

    Article  CAS  PubMed  Google Scholar 

  6. Ciardiello F, Tortora G (2008) EGFR antagonists in cancer treatment. N Engl J Med 358:1160–1174

    Article  CAS  PubMed  Google Scholar 

  7. 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 

  8. Mitsudomi T, Yatabe Y (2010) Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J 277:301–308

    Article  CAS  PubMed  Google Scholar 

  9. Pao W, Miller VA (2005) Epidermal growth factor receptor mutations, small-molecule kinase inhibitors, and non-small-cell lung cancer: current knowledge and future directions. J Clin Oncol 23:2556–2568

    Article  CAS  PubMed  Google Scholar 

  10. Cheng L, Alexander RE, Maclennan GT et al (2012) Molecular pathology of lung cancer: key to personalized medicine. Mod Pathol 25:347–369

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  12. Wong AT, To RM, Wong CL et al (2013) Evaluation of 2 real-time PCR assays for in vitro diagnostic use in the rapid and multiplex detection of EGFR gene mutations in NSCLC. Diagn Mol Pathol 22:138–143

    Article  CAS  PubMed  Google Scholar 

  13. Oxnard GR, Binder A, Janne PA (2013) New targetable oncogenes in non-small-cell lung cancer. J Clin Oncol 31:1097–1104

    Article  CAS  PubMed  Google Scholar 

  14. Sasaki T, Rodig SJ, Chirieac LR et al (2010) The biology and treatment of EML4-ALK non-small cell lung cancer. Eur J Cancer 46:1773–1780

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Koivunen JP, Mermel C, Zejnullahu K et al (2008) EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res 14:4275–4283

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Ma PC (2012) Personalized targeted therapy in advanced non-small cell lung cancer. Cleve Clin J Med 79(Electronic Suppl 1):eS56–eS60

    Article  PubMed  Google Scholar 

  17. Normanno N, Tejpar S, Morgillo F et al (2009) Implications for KRAS status and EGFR-targeted therapies in metastatic CRC. Nat Rev Clin Oncol 6:519–527

    Article  CAS  PubMed  Google Scholar 

  18. Russo A, Rizzo S, Bronte G et al (2009) The long and winding road to useful predictive factors for anti-EGFR therapy in metastatic colorectal carcinoma: the KRAS/BRAF pathway. Oncology 77(Suppl 1):57–68

    Article  CAS  PubMed  Google Scholar 

  19. Loupakis F, Ruzzo A, Cremolini C et al (2009) KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J Cancer 101:715–721

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. http://Somaticmutations-Egfr.Org/Nsclc.Html. Zugegriffen: 10. Mai 2013

  21. Custodio A, Feliu J (2013) Prognostic and predictive biomarkers for epidermal growth factor receptor-targeted therapy in colorectal cancer: beyond KRAS mutations. Crit Rev Oncol Hematol 85:45–81

    Article  PubMed  Google Scholar 

  22. Di Nicolantonio F, Martini M, Molinari F et al (2008) Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 26:5705–5712

    Article  Google Scholar 

  23. Caronia LM, Phay JE, Shah MH (2011) Role of BRAF in thyroid oncogenesis. Clin Cancer Res 17:7511–7517

    Article  CAS  PubMed  Google Scholar 

  24. Cantwell-Dorris ER, O’leary JJ, Sheils OM (2011) BRAFV600E: implications for carcinogenesis and molecular therapy. Mol Cancer Ther 10:385–394

    Article  CAS  PubMed  Google Scholar 

  25. Chapman PB, Hauschild A, Robert C et al (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364:2507–2516

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Merkelbach-Bruse S, Dietmaier W, Fuzesi L et al (2010) Pitfalls in mutational testing and reporting of common KIT and PDGFRA mutations in gastrointestinal stromal tumors. BMC Med Genet 11:106

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Tornillo L, Terracciano LM (2006) An update on molecular genetics of gastrointestinal stromal tumours. J Clin Pathol 59:557–563

    Article  CAS  PubMed  Google Scholar 

  28. Lopes LF, Bacchi CE (2010) Imatinib treatment for gastrointestinal stromal tumour (GIST). J Cell Mol Med 14:42–50

    Article  CAS  PubMed  Google Scholar 

  29. Corless CL, Barnett CM, Heinrich MC (2011) Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer 11:865–878

    CAS  PubMed  Google Scholar 

  30. Corless CL, Heinrich MC (2008) Molecular pathobiology of gastrointestinal stromal sarcomas. Annu Rev Pathol 3:557–586

    Article  CAS  PubMed  Google Scholar 

  31. Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2:127–137

    Article  CAS  PubMed  Google Scholar 

  32. Park JW, Neve RM, Szollosi J et al (2008) Unraveling the biologic and clinical complexities of HER2. Clin Breast Cancer 8:392–401

    Article  CAS  PubMed  Google Scholar 

  33. Bang YJ (2012) Advances in the management of HER2-positive advanced gastric and gastroesophageal junction cancer. J Clin Gastroenterol 46:637–648

    Article  CAS  PubMed  Google Scholar 

  34. Billah S, Stewart J, Staerkel G et al (2011) EGFR and KRAS mutations in lung carcinoma: molecular testing by using cytology specimens. Cancer Cytopathol 119:111–117

    Article  CAS  PubMed  Google Scholar 

  35. Fox EJ, Salk JJ, Loeb LA (2009) Cancer genome sequencing – an interim analysis. Cancer Res 69:4948–4950

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Gonzalez De Castro D, Clarke PA, Al-Lazikani B et al (2013) Personalized cancer medicine: molecular diagnostics, predictive biomarkers, and drug resistance. Clin Pharmacol Ther 93:252–259

    Article  Google Scholar 

  37. Suda K, Mizuuchi H, Maehara Y et al (2012) Acquired resistance mechanisms to tyrosine kinase inhibitors in lung cancer with activating epidermal growth factor receptor mutation – diversity, ductility, and destiny. Cancer Metastasis Rev 31:807–814

    Article  CAS  PubMed  Google Scholar 

Download references

Einhaltung ethischer Richtlinien

Interessenkonflikt. I. Bonzheim und F. Fend geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag enthält keine Studien an Menschen oder Tieren.

Author information

Authors and Affiliations

  1. Institut für Pathologie und Neuropathologie, Universitätsklinikum Tübingen und Comprehensive Cancer Center, Eberhard-Karls-Universität, Liebermeisterstr. 8, 72076, Tübingen, Deutschland

    I. Bonzheim & F. Fend

Authors
  1. I. Bonzheim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Fend
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to I. Bonzheim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bonzheim, I., Fend, F. Prädiktive Biomarker tumorrelevanter Signalwege in der molekularen Pathologie. Pathologe 35, 93–105 (2014). https://doi.org/10.1007/s00292-013-1798-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00292-013-1798-6

Schlüsselwörter

Keywords

Search

Navigation