KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program

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van Krieken J. H. J. M., Jung A., Kirchner T., Carneiro F., Seruca R., Bosman F. T., ...Daha Fazla

VIRCHOWS ARCHIV, cilt.453, sa.5, ss.417-431, 2008 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 453 Sayı: 5
  • Basım Tarihi: 2008
  • Doi Numarası: 10.1007/s00428-008-0665-y
  • Dergi Adı: VIRCHOWS ARCHIV
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.417-431
  • Anahtar Kelimeler: Colorectal carcinoma, Anti-EGFR therapy, KRAS mutation testing, Practice guidelines, Quality assurance, GROWTH-FACTOR-RECEPTOR, K-RAS MUTATIONS, CETUXIMAB SHOWS ACTIVITY, CANCER PATIENTS, MOLECULAR-MECHANISMS, CLINICAL-RESPONSE, DNA MUTATIONS, LUNG-CANCER, STOOL DNA, COLON
  • Ankara Üniversitesi Adresli: Evet

Özet

Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with colorectal carcinoma. However, these therapies are effective only in a subset of patients. Activating mutations in the KRAS gene are found in 30-40% of colorectal tumors and are associated with poor response to anti-EGFR therapies. Thus, KRAS mutation status can predict which patient may or may not benefit from anti-EGFR therapy. Although many diagnostic tools have been developed for KRAS mutation analysis, validated methods and standardized testing procedures are lacking. This poses a challenge for the optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Here we review the molecular basis of EGFR-targeted therapies and the resistance to treatment conferred by KRAS mutations. We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union.