best practice onkologie

, Volume 3, Issue 6, pp 48–58 | Cite as

Biomarker in der Onkologie

Diagnostik, Staging, Prognoseabschätzung und Therapie
CME · TOPIC · biomarker
  • 86 Downloads

Grundlagenforschung und translationale Forschung in der Onkologie konnten in den letzten Jahren eine Reihe von Biomarker identifizieren, die für Diagnostik, Staging, Prognoseabschätzung und als Ansatzpunkte für individualisierte Therapien potentiellen klinischen Wert haben. Einige dieser Marker sind bereits seit Jahren in die klinische Praxis eingeführt, andere werden derzeit im Rahmen wissenschaftlicher Programme an spezialisierten Krebszentren in der Praxis erprobt. Dieser Beitrag gibt einen Überblick klinisch etablierter Biomarker und einen Ausblick auf ausgewählte Kandidaten, die an der Schwelle zur breiten Anwendung stehen.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. 1.
    Geyer CE, Forster J, Lindquist D et al. (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med, 355: 2733–2743PubMedCrossRefGoogle Scholar
  2. 2.
    Press MF, Pike MC, Hung G et al. (1994) Amplification and overexpression of HER-2/neu in carcinomas of thesalivary gland: correlation with poor prognosis. Cancer Res, 54: 5675–5682PubMedGoogle Scholar
  3. 3.
    Romond EH, Perez EA, Bryant J et al. (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med, 353: 1673–1684PubMedCrossRefGoogle Scholar
  4. 4.
    MacGregor JI, JordanVC (1998) Basic guide to the mechanisms of antiestrogen action. Pharmacol Rev, 50: 151–196PubMedGoogle Scholar
  5. 5.
    Bonneterre J, Thurlimann B, Robertson JF et al. (2000) Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the tamoxifen or arimidex randomized group efficacy and tolerability study. J Clin Oncol, 18: 3748–3757PubMedGoogle Scholar
  6. 6.
    Rhodes A, Jasani B, Barnes DM et al. (2000) Reliability of immunohistochemical demonstration of oestrogen receptors in routine practice: interlaboratory variance in the sensitivity of detection and evaluation of scoring systems. J Clin Pathol, 53: 125–130PubMedCrossRefGoogle Scholar
  7. 7.
    Habel LA, Shak S, Jacobs MK et al. (2006) A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res, 8: R25PubMedCrossRefGoogle Scholar
  8. 8.
    Paik S, Shak S, Tang G et al. (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med, 351: 2817–2826PubMedCrossRefGoogle Scholar
  9. 9.
    Wolff AC, Hammond ME, Schwartz JN et al. (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med, 131: 18–43PubMedGoogle Scholar
  10. 10.
    Faratian D, Bartlett J (2008) Predictive markers in breast cancer – the future. Histopathology, 52: 91–98PubMedGoogle Scholar
  11. 11.
    Pritchard KI, Messersmith H, Elavathil L et al. (2008) HER-2 and topoisomerase II as predictors of response to chemotherapy. J Clin Oncol, 26: 736–744PubMedCrossRefGoogle Scholar
  12. 12.
    Knoop AS, Knudsen H, Balslev E et al. (2005) Rretrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group. J Clin Oncol, 23:Google Scholar
  13. 13.
    Tanner M, Jarvinen P, Isola J et al. (2001) Amplification of HER-2/neu and topoisomerase IIalpha in primary and metastatic breast cancer. Cancer Res, 61: 5345–5348PubMedGoogle Scholar
  14. 14.
    Nielsen KV, Ejlertsen B, Moller S et al. (2008) The value of TOP2A gene copy number variation as a biomarker in breast cancer: Update of DBCG trial 89D. Acta Oncol, 47: 725–734PubMedCrossRefGoogle Scholar
  15. 15.
    Tanner M, Isola J, Wiklund T et al. (2006) Topoisomerase IIalpha gene amplification predicts favorable treatment response to tailored and dose-escalated anthracycline-based adjuvant chemotherapy in HER-2/neu-amplified breast cancer: Scandinavian Breast Group Trial 9401. J Clin Oncol, 24: 2428–2436PubMedCrossRefGoogle Scholar
  16. 16.
    Sparano JA (2006) TAILORx: trial assigning individualized options for treatment (Rx). Clin Breast Cancer , 7: 347–350PubMedCrossRefGoogle Scholar
  17. 17.
    Goldstein LJ, Gray R, Badve S et al. (2008) Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features. J Clin Oncol , 26: 4063–4071PubMedCrossRefGoogle Scholar
  18. 18.
    Vijver MJ van de, He YD, Veer LJ van’t et al. (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med, 347: 1999–2009PubMedCrossRefGoogle Scholar
  19. 19.
    Veer LJ van’t, Dai H, Vijver MJ van de et al. (2002) Geneexpression profiling predicts clinical outcome of breast cancer. Nature, 415: 530–536CrossRefGoogle Scholar
  20. 20.
    Buyse M, Loi S, Veer L van’t et al. (2006) Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst, 98: 1183–1192PubMedCrossRefGoogle Scholar
  21. 21.
    Foekens JA, Atkins D, Zhang Y et al. (2006) Multicenter validation of a gene expression-based prognostic signature in lymph node-negative primary breast cancer. J Clin Oncol, 24: 1665–1671PubMedCrossRefGoogle Scholar
  22. 22.
    Wang Y, Klijn JG, Zhang Y et al. (2005) Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet, 365: 671–679PubMedGoogle Scholar
  23. 23.
    Druker BJ, Talpaz M, Resta DJ et al. (2001) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med, 344: 1031–1037PubMedCrossRefGoogle Scholar
  24. 24.
    Kantarjian H, Talpaz M, Estey E et al (1994) What is the contribution of molecular studies to the diagnosis of BCR-ABL-positive disease in adult acute leukemia? Am J Med, 96: 133–138PubMedCrossRefGoogle Scholar
  25. 25.
    Kurzrock R, Blick MB, Talpaz M et al. (1986) Rearrangement in the breakpoint cluster region and the clinical course in Philadelphia-negative chronic myelogenous leukemia. Ann Intern Med, 105: 673–679PubMedGoogle Scholar
  26. 26.
    Shtalrid M, Talpaz M, Blick M et al. (1988) Philadelphia-negative chronic myelogenous leukemia with breakpoint cluster region rearrangement: molecular analysis, clinical characteristics, and response to therapy. J Clin Oncol, 6: 1569–1575PubMedGoogle Scholar
  27. 27.
    Kurzrock R, Bueso-Ramos CE, Kantarjian H et al. (2001) BCR rearrangement-negative chronic myelogenous leukemia revisited. J Clin Oncol, 19: 2915–2926PubMedGoogle Scholar
  28. 28.
    Kurzrock R, Kantarjian HM, Shtalrid M et al. (1990) Philadelphia chromosome-negative chronic myelogenous leukemia without breakpoint cluster region rearrangement: a chronic myeloid leukemia with a distinct clinical course. Blood, 75: 445–452PubMedGoogle Scholar
  29. 29.
    Kantarjian H, Sawyers C, Hochhaus A et al. (2002) Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med, 346: 645–652PubMedCrossRefGoogle Scholar
  30. 30.
    Kantarjian HM, O’Brien S, Cortes J et al. (2003) Imatinib mesylate therapy improves survival in patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia in the chronic phase: comparison with historic data. Cancer, 98: 2636–2642PubMedCrossRefGoogle Scholar
  31. 31.
    Kantarjian HM, O’Brien S, Cortes JE et al. (2002) Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood, 100: 1590–1595PubMedGoogle Scholar
  32. 32.
    Reed SD, Anstrom KJ, Li Y, Schulman KA (2008) Updated estimates of survival and cost effectiveness for imatinib versus interferon-alpha plus low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukaemia. Pharmacoeconomics, 26: 435–446PubMedCrossRefGoogle Scholar
  33. 33.
    Reed SD, Anstrom KJ, Ludmer JA et al. (2004) Cost-effectiveness of imatinib versus interferon-alpha plus low-dose cytarabine for patients with newly diagnosed chronic-phase chronic myeloid leukemia. Cancer, 101: 2574–2583PubMedCrossRefGoogle Scholar
  34. 34.
    Kantarjian H, Giles F, Wunderle L et al. (2006) Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med, 354: 2542–2551PubMedCrossRefGoogle Scholar
  35. 35.
    Talpaz M, Shah NP, Kantarjian H et al. (2006) Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med , 354: 2531–2541PubMedCrossRefGoogle Scholar
  36. 36.
    Burger H, den Bakker MA, Kros JM et al. (2005) Activating mutations in c-KIT and PDGFRalpha are exclusively found in gastrointestinal stromal tumors and not in other tumors overexpressing these imatinib mesylate target genes. Cancer Biol Ther, 4: 1270–1274PubMedGoogle Scholar
  37. 37.
    Braconi C, Bracci R, Cellerino R (2008) Molecular targets in Gastrointestinal Stromal Tumors (GIST) therapy. Curr Cancer Drug Targets, 8: 359–366PubMedCrossRefGoogle Scholar
  38. 38.
    Vogelstein B, Fearon ER, Hamilton SR et al. (1988) Genetic alterations during colorectal-tumor development. N Engl J Med, 319: 525–532PubMedGoogle Scholar
  39. 39.
    Kastrinos F, Syngal S (2007) Recently identified colon cancer predispositions: MYH and MSH6 mutations. Semin Oncol, 34: 418–424PubMedCrossRefGoogle Scholar
  40. 40.
    Wang L, Baudhuin LM, Boardman LA et al. (2004) MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps. Gastroenterology, 127: 9-16PubMedCrossRefGoogle Scholar
  41. 41.
    Nielsen M, Franken PF, Reinards TH et al. (2005) Multiplicity in polyp count and extracolonic manifestations in 40 Dutch patients with MYH associated polyposis coli (MAP). J Med Genet, 42: e54PubMedCrossRefGoogle Scholar
  42. 42.
    Burt RW (2000) Colon cancer screening. Gastroenterology, 119: 837–853PubMedCrossRefGoogle Scholar
  43. 43.
    Lichtenstein P, Holm NV, Verkasalo PK et al. (2000) Environmental and heritable factors in the causation of cancer – analyses of cohorts of twins from Sweden, Denmark, and Finland. N EnglJ Med, 343: 78–85CrossRefGoogle Scholar
  44. 44.
    Ribic CM, Sargent DJ, Moore MJ et al. (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med, 349: 247–257PubMedCrossRefGoogle Scholar
  45. 45.
    Milano G, Etienne MC, Pierrefite V et al. (1999) Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity. Br J Cancer, 79: 627–630PubMedCrossRefGoogle Scholar
  46. 46.
    Ando Y, Saka H, Ando M et al. (2000) Polymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis. Cancer Res, 60: 6921–6926PubMedGoogle Scholar
  47. 47.
    Lord RV, Brabender J, Gandara D et al. (2002) Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res, 8: 2286–2291PubMedGoogle Scholar
  48. 48.
    Cunningham D, Humblet Y, Siena S et al. (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med, 351: 337–345PubMedCrossRefGoogle Scholar
  49. 49.
    Personeni N, Fieuws S, Piessevaux H et al. (2008) Clinical usefulness of EGFR gene copy number as a predictive marker in colorectal cancer patients treated with cetuximab: a fluorescent in situ hybridization study. Clin Cancer Res, 14: 5869–5876PubMedCrossRefGoogle Scholar
  50. 50.
    Lievre A, Bachet JB, Boige V et al. (2008) KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol, 26: 374–379PubMedCrossRefGoogle Scholar
  51. 51.
    Maheswaran S, Sequist LV, Nagrath S et al. (2008) Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med, 359: 366–377PubMedCrossRefGoogle Scholar
  52. 52.
    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: 2747–2754PubMedCrossRefGoogle Scholar
  53. 53.
    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: 983–991PubMedCrossRefGoogle Scholar
  54. 54.
    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: 4731–4737PubMedCrossRefGoogle Scholar
  55. 55.
    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: 2741–2746PubMedCrossRefGoogle Scholar
  56. 56.
    Monzo M, Rosell R, Sanchez JJ et al. (1999) Paclitaxel resistance in non-small-cell lung cancer associated with beta-tubulin gene mutations. J Clin Oncol, 17: 1786–1793PubMedGoogle Scholar
  57. 57.
    Cappuzzo F, Ligorio C, Janne PA et al. (2007) Prospective study of gefitinib in epidermal growth factor receptor fluorescence in situ hybridization-positive/phospho-Akt-positive or never smoker patients with advanced non-small-cell lung cancer: the ONCOBELL trial. J Clin Oncol, 25: 2248–2255PubMedCrossRefGoogle Scholar
  58. 58.
    Han SW, Kim TY, Jeon YK et al. (2006) Optimization of patient selection for gefitinib in non-small cell lung cancer by combined analysis of epidermal growth factor receptor mutation, K-ras mutation, and Akt phosphorylation. Clin Cancer Res, 12: 2538–2544PubMedCrossRefGoogle Scholar
  59. 59.
    Mounawar M, Mukeria A, Le Calvez F et al. (2007) Patterns of EGFR, HER2, TP53, and KRAS mutations of p14arf expression in non-small cell lung cancers in relation to smoking history. Cancer Res, 67: 5667–5672PubMedCrossRefGoogle Scholar
  60. 60.
    Belani CP, Schreeder MT, Steis RG et al. (2008) Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced-stage nonsmall cell lung cancer: a multicenter phase 2 study. Cancer, 113: 2512–2517PubMedCrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag 2008

Authors and Affiliations

  1. 1.Innere Klinik (Tumorforschung), Westdeutsches TumorzentrumUniversitätsklinikum EssenEssenGermany
  2. 2.Innere Klinik (Tumorforschung) , Westdeutsches TumorzentrumUniversitätsklinikum EssenEssenGermany
  3. 3.Innere Klinik (Tumorforschung) , Westdeutsches TumorzentrumUniversitätsklinikum EssenEssenGermany

Personalised recommendations