KRAS mutation testing of colorectal cancer for anti-EGFR therapy: Dogmas versus evidence

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

KRAS mutation testing opened up a new era in routine pathological diagnostics of colorectal cancer similar to the introduction of HER-2 testing in breast cancer with the significant difference that mutational analysis exclusively relies on molecular methodologies. In order to critically analyze the current rational of KRAS mutation testing in colorectal carcinoma we have performed evaluation of related articles available in PubMed/Medline, Society recommendations, anti-EGFR antibody registration documents and NCCN guidelines. KRAS mutation is frequent in colorectal cancer and data suggest a negative prognostic, but neutral predictive significance, with the exception of its strong negative predictive value in case of anti-EGFR antibody therapies. However, there is only scattered information on the significance of rare mutations and copy number changes of KRAS. Furthermore, other mutations in EGFR signaling pathway may also have predictive value such as BRAF, PIK3CA or PTEN. It also seems to be a critical issue whether the K-RAS testing must be done on primary, regional or distant metastatic tissues: data already suggest a small but significant chance of alteration during tumor progression. Technically KRAS mutation testing can be performed by various methods characterized by different sensitivities and specificities, although the clinical significance of these parameters are unknown at the present. The consensus strongly suggests the need for an effective quality control program for these methods. KRAS mutation testing in colorectal cancer raised fundamental biological, clinical and molecular pathological questions as it has become a standard application for predicting sensitivity for anti-EGFR antibody therapies. However, these questions can only be answered by rigorous, dogma-free preclinical and clinical studies.

Original languageEnglish
Pages (from-to)813-823
Number of pages11
JournalCurrent cancer drug targets
Volume10
Issue number8
DOIs
Publication statusPublished - Jan 1 2010

    Fingerprint

Keywords

  • Anti-EGFR therapy
  • Colorectal cancer
  • KRAS
  • Mutation analysis

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Drug Discovery
  • Cancer Research

Cite this