Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular and Clinical Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9450 Online ISSN: 2049-9469
Journal Cover
May-June 2014 Volume 2 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-June 2014 Volume 2 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

KRAS mutation in patients with metastatic colorectal cancer does not preclude benefit from oxaliplatin‑ or irinotecan‑based treatment

  • Authors:
    • Hiroshi Soeda
    • Hideki Shimodaira
    • Mika Watanabe
    • Takao Suzuki
    • Makio Gamo
    • Masanobu Takahashi
    • Keigo Komine
    • Shunsuke Kato
    • Chikashi Ishioka
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980‑8575, Japan, Department of Pathology, Tohoku University Hospital, Sendai, Miyagi 980‑8574, Japan, Department of Medical Oncology, Sendai Medical Center, Sendai, Miyagi 983‑8520, Japan, Department of Clinical Oncology, South Miyagi Medical Center, Ogawara, Miyagi 989‑1253, Japan
  • Pages: 356-362
    |
    Published online on: February 10, 2014
       https://doi.org/10.3892/mco.2014.254
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Fluoropyrimidine‑based chemotherapy plus antibody therapy is currently the standard first‑line treatment for metastatic colorectal cancer (mCRC). In this study, we investigated the hypothesis that mutations in several of the targeted oncogenes are correlated with treatment outcomes in mCRC patients receiving different first‑line regimens. Our study included a total of 194 patients who had undergone various forms of first‑line chemotherapy. The KRAS, BRAF, PIK3CA, NRAS and AKT1 mutational status of the tumors was assessed and the association between mutational status and treatment outcome was evaluated. The median progression‑free survival (mPFS) of the wild‑type and mutated KRAS subgroups that had received oxaliplatin‑based treatment was 8.6 and 6.8 months, respectively (P=0.41), whereas the mPFS of the wild‑type KRAS, BRAF, PIK3CA, NRAS and AKT1 subgroups and that of their respective mutant subgroups was 9.7 and 7.2 months, respectively (P=0.10). The mPFS of the wild‑type and mutated KRAS subgroups that had received irinotecan‑based treatments was 7.7 and 9.7 months, respectively (P=0.43). The mPFS of the wild‑type KRAS, BRAF, PIK3CA, NRAS and AKT1 subgroups and that of their respective mutant subgroups was 7.1 and 10.0 months, respectively (P=0.76). Our data indicated that mCRC patients with activation of KRAS, BRAF, PIK3CA, NRAS and AKT1 mutations, even those being treated with oxaliplatin‑ and irinotecan‑based regimens as first‑line treatment, may benefit from cytotoxic drug therapy.
View Figures

Figure 1

Figure 2

View References

1. 

Van Cutsem E, Kohne CH, Hitre E, et al: Cetuximab and chemo-therapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 360:1408–1417. 2009.PubMed/NCBI

2. 

Bokemeyer C, Bondarenko I, Makhson A, et al: Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 27:663–671. 2009. View Article : Google Scholar : PubMed/NCBI

3. 

Hurwitz H, Fehrenbacher L, Novotny W, et al: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 350:2335–2342. 2004. View Article : Google Scholar : PubMed/NCBI

4. 

Cunningham D, Humblet Y, Siena S, et al: Cetuximab mono-therapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 351:337–345. 2004. View Article : Google Scholar : PubMed/NCBI

5. 

Bos JL, Fearon ER, Hamilton SR, et al: Prevalence of ras gene mutations in human colorectal cancers. Nature. 327:293–297. 1987. View Article : Google Scholar : PubMed/NCBI

6. 

Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, et al: Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res. 67:2643–2648. 2007. View Article : Google Scholar

7. 

Di Fiore F, Blanchard F, Charbonnier F, et al: Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by cetuximab plus chemotherapy. Br J Cancer. 96:1166–1169. 2007.PubMed/NCBI

8. 

Amado RG, Wolf M, Peeters M, et al: Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 26:1626–1634. 2008. View Article : Google Scholar : PubMed/NCBI

9. 

Hecht JR, Mitchell E, Chidiac T, et al: A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol. 27:672–680. 2009. View Article : Google Scholar : PubMed/NCBI

10. 

Van Cutsem E, Lang I, D’haens G, et al: KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: the CRYSTAL experience. J Clin Oncol. 26:abstract 2. 2008.PubMed/NCBI

11. 

Punt CJ, Tol J, Rodenburg CJ, et al: Randomized phase III study of capecitabine, oxaliplatin, and bevacizumab with or without cetuximab in advanced colorectal cancer (ACC), the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). J Clin Oncol. 26:abstract LBA4011. 2008.PubMed/NCBI

12. 

Bokemeyer C, Bondarenko I, Hartmann JT, et al: KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without cetuximab: the OPUS experience. J Clin Oncol. 26:abstract 4000. 2008.

13. 

Karapetis CS, Khambata-Ford S, Jonker DJ, et al: K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 359:1757–1765. 2008. View Article : Google Scholar : PubMed/NCBI

14. 

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

15. 

Tol J, Nagtegaal ID and Punt CJ: BRAF mutation in metastatic colorectal cancer. N Engl J Med. 361:98–99. 2009. View Article : Google Scholar : PubMed/NCBI

16. 

De Roock W, Claes B, Bernasconi D, et al: Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory meta-static colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 11:753–762. 2010.PubMed/NCBI

17. 

Watanabe T, Yoshino T, Uetake H, et al: KRAS mutational status in Japanese patients with colorectal cancer: results from a nationwide, multicenter, cross-sectional study. Jpn J Clin Oncol. 43(7): 706–712. 2013. View Article : Google Scholar : PubMed/NCBI

18. 

Andreyev HJ, Norman AR, Cunningham D, et al: Kirsten ras mutations in patients with colorectal cancer: the multicenter ‘RASCAL’ study. J Natl Cancer Inst. 90:675–684. 1998.

19. 

Andreyev HJ, Norman AR, Cunningham D, et al: Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study. Br J Cancer. 85:692–696. 2001.

20. 

Barault L, Veyrie N, Jooste V, et al: Mutations in the RAS-MAPK, PI(3)K (phosphatidylinositol-3-OH kinase) signaling network correlate with poor survival in a population-based series of colon cancers. Int J Cancer. 122:2255–2259. 2008. View Article : Google Scholar : PubMed/NCBI

21. 

Ogino S, Nosho K, Kirkner GJ, et al: PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer. J Clin Oncol. 27:1477–1484. 2009. View Article : Google Scholar : PubMed/NCBI

22. 

Carpten JD, Faber AL, Horn C, et al: A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature. 448:439–444. 2007. View Article : Google Scholar : PubMed/NCBI

23. 

Sartore-Bianchi A, Martini M, Molinari F, et al: PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Research. 69:1851–1857. 2009. View Article : Google Scholar : PubMed/NCBI

24. 

Ince WL, Jubb AM, Holden SN, et al: Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab. J Natl Cancer Inst. 97:981–989. 2005. View Article : Google Scholar : PubMed/NCBI

25. 

Hurwitz HI, Yi J, Ince W, et al: The clinical benefit of bevacizumab in metastatic colorectal cancer is independent of K-ras mutation status: analysis of a phase III study of bevacizumab with chemotherapy in previously untreated metastatic colorectal cancer. Oncologist. 14:22–28. 2009. View Article : Google Scholar

26. 

Richman SD, Seymour MT, Chambers P, et al: KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial. J Clin Oncol. 27:5931–5937. 2009. View Article : Google Scholar : PubMed/NCBI

27. 

Souglakos J, Philips J, Wang R, et al: Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer. 101:465–472. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Soeda H, Shimodaira H, Watanabe M, Suzuki T, Gamo M, Takahashi M, Komine K, Kato S and Ishioka C: KRAS mutation in patients with metastatic colorectal cancer does not preclude benefit from oxaliplatin‑ or irinotecan‑based treatment. Mol Clin Oncol 2: 356-362, 2014.
APA
Soeda, H., Shimodaira, H., Watanabe, M., Suzuki, T., Gamo, M., Takahashi, M. ... Ishioka, C. (2014). KRAS mutation in patients with metastatic colorectal cancer does not preclude benefit from oxaliplatin‑ or irinotecan‑based treatment. Molecular and Clinical Oncology, 2, 356-362. https://doi.org/10.3892/mco.2014.254
MLA
Soeda, H., Shimodaira, H., Watanabe, M., Suzuki, T., Gamo, M., Takahashi, M., Komine, K., Kato, S., Ishioka, C."KRAS mutation in patients with metastatic colorectal cancer does not preclude benefit from oxaliplatin‑ or irinotecan‑based treatment". Molecular and Clinical Oncology 2.3 (2014): 356-362.
Chicago
Soeda, H., Shimodaira, H., Watanabe, M., Suzuki, T., Gamo, M., Takahashi, M., Komine, K., Kato, S., Ishioka, C."KRAS mutation in patients with metastatic colorectal cancer does not preclude benefit from oxaliplatin‑ or irinotecan‑based treatment". Molecular and Clinical Oncology 2, no. 3 (2014): 356-362. https://doi.org/10.3892/mco.2014.254
Copy and paste a formatted citation
x
Spandidos Publications style
Soeda H, Shimodaira H, Watanabe M, Suzuki T, Gamo M, Takahashi M, Komine K, Kato S and Ishioka C: KRAS mutation in patients with metastatic colorectal cancer does not preclude benefit from oxaliplatin‑ or irinotecan‑based treatment. Mol Clin Oncol 2: 356-362, 2014.
APA
Soeda, H., Shimodaira, H., Watanabe, M., Suzuki, T., Gamo, M., Takahashi, M. ... Ishioka, C. (2014). KRAS mutation in patients with metastatic colorectal cancer does not preclude benefit from oxaliplatin‑ or irinotecan‑based treatment. Molecular and Clinical Oncology, 2, 356-362. https://doi.org/10.3892/mco.2014.254
MLA
Soeda, H., Shimodaira, H., Watanabe, M., Suzuki, T., Gamo, M., Takahashi, M., Komine, K., Kato, S., Ishioka, C."KRAS mutation in patients with metastatic colorectal cancer does not preclude benefit from oxaliplatin‑ or irinotecan‑based treatment". Molecular and Clinical Oncology 2.3 (2014): 356-362.
Chicago
Soeda, H., Shimodaira, H., Watanabe, M., Suzuki, T., Gamo, M., Takahashi, M., Komine, K., Kato, S., Ishioka, C."KRAS mutation in patients with metastatic colorectal cancer does not preclude benefit from oxaliplatin‑ or irinotecan‑based treatment". Molecular and Clinical Oncology 2, no. 3 (2014): 356-362. https://doi.org/10.3892/mco.2014.254
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team