Molekulare Charakterisierung des Pankreaskarzinoms

Therapeutische Implikationen
  • C. Benedikt WestphalenEmail author
  • Kathrin Heinrich
  • Stefan Böck
  • Volker Heinemann



Die Präzisionsonkologie erzielt mittlerweile große Erfolge in einer Vielzahl von malignen Erkrankungen. Basierend auf umfassender molekularer Charakterisierung konnte die Behandlungsrealität vieler Tumorerkrankungen entscheiden verändert, teils revolutioniert werden. Auch das Verständnis um die molekulare Pathologie des Bauchspeicheldrüsenkarzinoms hat in den vergangenen Jahren deutlich zugenommen. Ziel dieses Beitrags ist, mögliche präzisionsonkologische Ansätze in der Behandlung des Pankreaskarzinoms zu erläutern.


Das bessere Verständnis um die molekulare Pathologie des Pankreaskarzinoms hat aktuell noch keinen entscheidenden Einfluss auf dessen therapeutische Realität und hat sich dementsprechend noch nicht auf die weiterhin schlechte Prognose dieser Entität ausgewirkt. Nichtsdestotrotz können auch heute bereits Patienten mit Bauchspeicheldrüsenkrebs von erweiterter molekularer Diagnostik profitieren.


Präzisionsonkologie Molekulare Diagnostik Zielgerichtete Therapie Tumorerkrankungen Molekulare Pathologie 

Molecular characterization of pancreatic cancer

Therapeutic implications



Precision oncology has achieved significant successes in the treatment of many malignant diseases. Based on comprehensive molecular profiling the treatment reality of many tumors has been decisively changed and in part been revolutionized. Along the same lines, there is a growing body of knowledge with respect to the molecular pathology of pancreatic cancer. The aim of this article is to briefly outline potential therapeutic strategies to implement precision oncology in the treatment of pancreatic cancer.


While there is growing knowledge about the molecular pathology of pancreatic cancer, this knowledge has not been translated into a change in management or an improvement of the dismal prognosis of pancreatic cancer. Nevertheless, even today some patients with pancreatic cancer might profit from extended molecular diagnostics.


Precision cancer medicine Molecular diagnostics Targeted therapies Tumor diseases Molecular pathology 


Einhaltung ethischer Richtlinien


C. B. Westphalen, K. Heinrich, S. Böck und V. Heinemann geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.


  1. 1.
    Garrido-Laguna I, Hidalgo M (2015) Pancreatic cancer: from state-of-the-art treatments to promising novel therapies. Nat Rev Clin Oncol 12(6):319–334CrossRefGoogle Scholar
  2. 2.
    Rahib L et al (2014) Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 74:2913. CrossRefPubMedGoogle Scholar
  3. 3.
    Quante AS et al (2016) Projections of cancer incidence and cancer-related deaths in Germany by 2020 and 2030. Cancer Med 5(9):2649–2656CrossRefGoogle Scholar
  4. 4.
    Vaccaro V, Sperduti I, Milella M (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 365(8):768–769 (author reply 769)CrossRefGoogle Scholar
  5. 5.
    Von Hoff DD et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369(18):1691–1703CrossRefGoogle Scholar
  6. 6.
    Conroy T et al (2018) FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med 379(25):2395–2406CrossRefGoogle Scholar
  7. 7.
    Oberstein PE, Olive KP (2013) Pancreatic cancer: why is it so hard to treat? Therap Adv Gastroenterol 6(4):321–337CrossRefGoogle Scholar
  8. 8.
    Hirsch FR et al (2017) Lung cancer: current therapies and new targeted treatments. Lancet 389(10066):299–311CrossRefGoogle Scholar
  9. 9.
    Le DT et al (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372(26):2509–2520CrossRefGoogle Scholar
  10. 10.
    Laetsch TW et al (2018) Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol 19(5):705–714CrossRefGoogle Scholar
  11. 11.
    Drilon A et al (2017) Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK inhibitor entrectinib: combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov 7(4):400–409CrossRefGoogle Scholar
  12. 12.
    Drilon AE et al (2018) A phase 1 study of LOXO-292, a potent and highly selective RET inhibitor, in patients with RET-altered cancers. J Clin Oncol 36(15_suppl):102–102CrossRefGoogle Scholar
  13. 13.
    Jones S et al (2008) Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321(5897):1801–1806CrossRefGoogle Scholar
  14. 14.
    Collisson EA et al (2011) Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat Med 17(4):500–503CrossRefGoogle Scholar
  15. 15.
    Waddell N et al (2015) Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 518(7540):495–501CrossRefGoogle Scholar
  16. 16.
    Roberts NJ et al (2016) Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer. Cancer Discov 6(2):166–175CrossRefGoogle Scholar
  17. 17.
    Bailey P et al (2016) Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531:47–52CrossRefGoogle Scholar
  18. 18.
    Cancer Genome Atlas Research Network (2017) Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell 32(2):185–203.e13CrossRefGoogle Scholar
  19. 19.
    Muckenhuber A et al (2018) Pancreatic ductal adenocarcinoma subtyping using the biomarkers hepatocyte nuclear factor-1A and cytokeratin-81 correlates with outcome and treatment response. Clin Cancer Res 24(2):351–359CrossRefGoogle Scholar
  20. 20.
    Krantz BA, O’Reilly EM (2018) Biomarker-based therapy in pancreatic ductal adenocarcinoma: an emerging reality? Clin Cancer Res 24(10):2241–2250CrossRefGoogle Scholar
  21. 21.
    Lowery MA et al (2018) Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms. J Natl Cancer Inst 110:1067–1074. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Cristescu R et al (2018) Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science 362(6411):eaar3593CrossRefGoogle Scholar
  23. 23.
    Hu ZI et al (2018) Evaluating mismatch repair deficiency in pancreatic adenocarcinoma: challenges and recommendations. Clin Cancer Res 24(6):1326–1336CrossRefGoogle Scholar
  24. 24.
    Vanderwalde A et al (2018) Microsatellite instability status determined by next-generation sequencing and compared with PD-L1 and tumor mutational burden in 11,348 patients. Cancer Med 7(3):746–756CrossRefGoogle Scholar
  25. 25.
    Le Tourneau C et al (2015) Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol 16(13):1324–1334CrossRefGoogle Scholar
  26. 26.
    Massard C et al (2017) High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the MOSCATO 01 trial. Cancer Discov 7(6):586–595CrossRefGoogle Scholar
  27. 27.
    Subbiah V, Kurzrock R (2017) Debunking the delusion that precision oncology is an illusion. Oncologist 22(8):881–882CrossRefGoogle Scholar
  28. 28.
    Prasad V (2016) Perspective: the precision-oncology illusion. Nature 537(7619):S63CrossRefGoogle Scholar
  29. 29.
    Verlingue L et al (2017) Precision medicine for patients with advanced biliary tract cancers: an effective strategy within the prospective MOSCATO-01 trial. Eur J Cancer 87:122–130CrossRefGoogle Scholar
  30. 30.
    Schwaederle M et al (2016) Association of biomarker-based treatment strategies with response rates and progression-free survival in refractory malignant neoplasms: a meta-analysis. Jama Oncol 2(11):1452–1459CrossRefGoogle Scholar
  31. 31.
    Aung KL et al (2018) Genomics-driven precision medicine for advanced pancreatic cancer: early results from the COMPASS trial. Clin Cancer Res 24(6):1344–1354CrossRefGoogle Scholar
  32. 32.
    Lowery MA et al (2017) Real-time genomic profiling of pancreatic ductal adenocarcinoma: potential actionability and correlation with clinical phenotype. Clin Cancer Res 23(20):6094–6100CrossRefGoogle Scholar
  33. 33.
    Heining C et al (2018) NRG1 fusions in KRAS wild-type pancreatic cancer. Cancer Discov 8(9):1087–1095CrossRefGoogle Scholar
  34. 34.
    Alistar A et al (2017) Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial. Lancet Oncol 18(6):770–778CrossRefGoogle Scholar
  35. 35.
    Bailey P et al (2016) Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531:47–52. CrossRefPubMedGoogle Scholar
  36. 36.
    Dreyer SB, Bailey DKCP, Andrew V (2017) Biankin pancreatic cancer genomes: implications for clinical management and therapeutic development. Clin Cancer Res 23(7):1CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  • C. Benedikt Westphalen
    • 1
    Email author
  • Kathrin Heinrich
    • 1
  • Stefan Böck
    • 1
  • Volker Heinemann
    • 1
  1. 1.Medizinische Klinik und Poliklinik III, Klinikum der Universität München, Großhadern und Comprehensive Cancer Center MünchenLMUMünchenDeutschland

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