Skip to main content
SpringerLink
Log in

Stellenwert der BRAF-Inhibition bei soliden Tumoren wie dem kolorektalen Karzinom

Role of BRAF inhibitors in solid tumors such as colorectal cancer

  • Leitthema
  • Published:
Der Onkologe Aims and scope

Zusammenfassung

Hintergrund

BRAF-V600E-mutierte kolorektale Karzinome (KRK) sind mit 8–12 % aller KRK vergleichsweise selten. In der metastasierten Situation ist diese Mutation prognostisch sehr ungünstig.

Material und Methoden

Relevante Literatur wurde ausgewertet und zusammenfassend dargestellt.

Ergebnisse

Auch bei Behandlung mit intensivierter Chemotherapie sind die Überlebenszeiten von Patienten mit BRAF-V600E-mutierten Tumoren am geringsten von allen KRK-Subtypen.

Schlussfolgerung

Innovative Behandlungskonzepte, die sich auf unterschiedliche Komponenten des EGFR-RAS-RAF-MEK-ERK-Signalwegs richten, definieren einen neuen Therapiestandard für diese Subgruppe metastasierter KRK.

Abstract

Background

BRAFV600E-mutated colorectal cancer (CRC) is comparatively rare with an incidence of 8–12% of all CRCs. In the metastatic setting, this mutation is associated with a particularly poor prognosis.

Materials and methods

The relevant literature was evaluated and summarized.

Results

Even when treated with intensified chemotherapy, overall survival of patients with BRAFV600E-mutated mCRC is the poorest of all CRC subtypes.

Conclusion

Novel therapeutic concepts that target several components of the EGFR-RAS-RAF-MEK-ERK signaling pathway define a new treatment standard for this subgroup of metastatic CRCs.

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

Literatur

  1. Robert Koch-Institut (2017) Krebs in Deutschland für 2013/2014 https://doi.org/10.17886/rkipubl-2017-007

    Book  Google Scholar 

  2. Bruckner HW, Motwani BT (1991) Chemotherapy of advanced cancer of the colon and rectum. Semin Oncol 18(5):443–461

    CAS  PubMed  Google Scholar 

  3. Tournigand C et al (2004) FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 22(2):229–237

    Article  CAS  Google Scholar 

  4. Hurwitz H et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342

    Article  CAS  Google Scholar 

  5. Bokemeyer C et al (2009) Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 27(5):663–671

    Article  CAS  Google Scholar 

  6. Heinemann V, von Weikersthal LF, Decker T et al (2014) FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastastic colorectal cancer (FIRE-3): a randomized, open-label, phase 3 trial. Lancet Oncol 15:1065–1075

    Article  CAS  Google Scholar 

  7. Douillard JY et al (2013) Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 369(11):1023–1034

    Article  CAS  Google Scholar 

  8. Van Cutsem E et al (2015) Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol 33(7):692–700

    Article  Google Scholar 

  9. Tran B et al (2011) Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer 117(20):4623–4632

    Article  CAS  Google Scholar 

  10. Tveit KM et al (2012) Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol 30(15):1755–1762

    Article  CAS  Google Scholar 

  11. Pietrantonio F et al (2015) Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: a meta-analysis. Eur J Cancer 51(5):587–594

    Article  CAS  Google Scholar 

  12. Venderbosch S et al (2014) Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res 20(20):5322–5330

    Article  CAS  Google Scholar 

  13. Deng G, Bell I, Crawley S et al (2004) BRAF mutation is frequently present in sporadic colorectal cancer with methylated hMLH1, but not in hereditary nonpolyposis colorectal cancer. Clin Cancer Res 10:191–195

    Article  CAS  Google Scholar 

  14. Samowitz WS, Sweeney C, Herrick J et al (2005) Poor survival associated with the BRAF V600E mutation in microsatellite stable colon cancers. Cancer Res 65(14):6063–6069

    Article  CAS  Google Scholar 

  15. Cremolini C et al (2015) BRAF codons 594 and 596 mutations identify a new molecular subtype of metastatic colorectal cancer at favorable prognosis. Ann Oncol 26(10):2092–2097

    Article  CAS  Google Scholar 

  16. Loupakis F et al (2014) FOLFOXIRI plus bevacizumab as first-line treatment in BRAF mutant metastatic colorectal cancer. Eur J Cancer 50(1):57–63

    Article  CAS  Google Scholar 

  17. Kopetz S et al (2015) Phase II pilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer. J Clin Oncol 33(34):4032–4038

    Article  CAS  Google Scholar 

  18. Samalin E, Bouche O, Thezenas S et al (2014) Sorafenib and irinotecan (NEXIRI) as second- or later-line treatment for patients with metastastic colorectal cancer and KRAS-mutated tumours: a multicenter Phase I/II trial. Br J Cancer 110:1148–1154

    Article  CAS  Google Scholar 

  19. Kopetz S, Desai J, Chan E et al (2015) Phase II pilot study of vemurafenib in patients with metastastic BRAF-mutated colorectal cancer. J Clin Oncol 33:4032–4038

    Article  CAS  Google Scholar 

  20. Hyman DM, Puzanov I, Subbiah V et al (2015) Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med 373:726–736

    Article  CAS  Google Scholar 

  21. Chen SH, Zhang Q, Van Horn RD et al (2016) Oncogenic BRAF deletions that function as homodimers and are sensitive ton inhibition by RAF dimer inhibitor LY3009120. Cancer Discov 6:300–315

    Article  CAS  Google Scholar 

  22. Vakana E, Pratt S, Blosser W et al (2017) LY3009120, a panRAF inhibitor, has significant anti-tumor activity in BRAF and KRAS mutant preclinical models of colorectal cancer. Oncotarget 8:9251–9266

    Article  Google Scholar 

  23. Corcoran RB, Atreya CE, Falchook GS et al (2015) Combined BRAF and MEK inhibition with dabrafenib and trametinib in BRAF V600-mutant colorectal cancer. J Clin Oncol 112:1921–1928

    Google Scholar 

  24. Corcoran RB, Ebi H, Turke AB et al (2012) EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib. Cancer Discov 2:227–235

    Article  CAS  Google Scholar 

  25. Corcoran RB, Andre T, Attreya CE et al (2018) Combined BRAF, EGFR, and MEK inhibition in patients with BRAF(V600E)-mutant colorectal cancer. Cancer Discov 8:428–443

    Article  CAS  Google Scholar 

  26. Kopetz S, McDonough SL, Morris VK et al (2017) Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG 1406). J Clin Oncol 35(Suppl 4S):520

    Article  Google Scholar 

  27. Kopetz S, Grothey A, Yaeger E et al (2019) Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N Eng J Med 381(17):1632–1643

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Innere Medizin I, Universitätsklinikum Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Deutschland

    Melanie Güthle &  Thomas Seufferlein

Authors
  1. Melanie Güthle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Seufferlein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Seufferlein.

Ethics declarations

Interessenkonflikt

M. Güthle und T. Seufferlein geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Güthle, M., Seufferlein, T. Stellenwert der BRAF-Inhibition bei soliden Tumoren wie dem kolorektalen Karzinom. Onkologe 26, 708–712 (2020). https://doi.org/10.1007/s00761-020-00785-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00761-020-00785-8

Schlüsselwörter

Keywords

Search

Navigation