The long and winding road to useful predictive factors for anti-EGFR therapy in metastatic colorectal carcinoma: the KRAS/BRAF pathway

Oncology
Antonio RussoFabio Fulfaro

Abstract

Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with metastatic colorectal carcinoma. Among patients not carrying activating mutations in the KRAS gene, only a limited number will experience tumor response to these therapeutic agents. The role of BRAF mutations in determining resistance to this treatment is emerging through preclinical and clinical studies. Standardization and validation of laboratory mutation analysis is needed to allow an optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Clinical single-arm and randomized studies were conducted both in first-line and refractory settings to evaluate the correlation of KRAS mutational status and efficacy of cetuximab and panitumumab. The main trials on first-line regiments are CRYSTAL, which is looking at FOLFIRI (folinic acid, fluorouracil, irinotecan) + cetuximab, and OPUS, which is evaluating FOLFOX (folinic acid, fluorouracil, oxaliplatin) + cetuximab. The results of these trials have induced the European Medicines Agency to apply restrictions to its approval of cetuximab and panitumumab for use in metastatic colorectal cancer patients with wild-type KRAS tumors. However, the absence...Continue Reading

Citations

Mar 16, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·Y BalagulaM E Lacouture
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Jun 25, 2014·Expert Review of Gastroenterology & Hepatology·Christian RolfoMarc Peeters
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Aug 9, 2020·Cancer Investigation·Dong Hae JungWon-Suk Lee
Nov 16, 2019·Biomarkers in Medicine·XiuLan LiuZhiHui Yang
Oct 22, 2020·Expert Review of Gastroenterology & Hepatology·Cristina SmolenschiMichel Ducreux
Dec 19, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Stephanie M CushmanAndrew B Nixon

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