BACKGROUND: The epidermal growth factor receptor (EGFR) is an important target in the treatment of metastatic colorectal carcinoma (mCRC). The combination of anti-EGFR antibodies with chemotherapy has led to a higher response rate of certain kinds of tumor as well as a significant prolongation of the progression-free interval. The KRAS protein is an important mediator in the signal transduction cascade regulated by the EGFR. A KRAS mutation is present in 30% to 49% of all colorectal carcinomas. Mutations in the KRAS gene can be demonstrated by the methods of molecular pathology and are a very important factor in the selection of molecular biological treatment options targeted against EGFR. METHODS: Selective literature review. RESULTS: Patients bearing mutations of the KRAS gene do not benefit from treatment with the EGFR antibodies cetuximab and panitumumab. CONCLUSIONS: Activating mutations of the KRAS gene are biomarkers for resistance to cetuximab or panitumumab. Thus, anti-EGFR therapies are approved for the treatment of metastatic colorectal carcinoma only on condition that the mutation state of the KRAS gene is determined first, because the combination of chemotherapy with anti-EGFR is expected to increase the response rate only in patients with the wild-type KRAS gene.
BACKGROUND: The epidermal growth factor receptor (EGFR) is an important target in the treatment of metastatic colorectal carcinoma (mCRC). The combination of anti-EGFR antibodies with chemotherapy has led to a higher response rate of certain kinds of tumor as well as a significant prolongation of the progression-free interval. The KRAS protein is an important mediator in the signal transduction cascade regulated by the EGFR. A KRAS mutation is present in 30% to 49% of all colorectal carcinomas. Mutations in the KRAS gene can be demonstrated by the methods of molecular pathology and are a very important factor in the selection of molecular biological treatment options targeted against EGFR. METHODS: Selective literature review. RESULTS:Patients bearing mutations of the KRAS gene do not benefit from treatment with the EGFR antibodies cetuximab and panitumumab. CONCLUSIONS: Activating mutations of the KRAS gene are biomarkers for resistance to cetuximab or panitumumab. Thus, anti-EGFR therapies are approved for the treatment of metastatic colorectal carcinoma only on condition that the mutation state of the KRAS gene is determined first, because the combination of chemotherapy with anti-EGFR is expected to increase the response rate only in patients with the wild-type KRAS gene.
Entities:
Keywords:
cancer therapy; cetuximab; colorectal carcinoma; gene mutation; molecular medicine
Authors: M Esteller; S González; R A Risques; E Marcuello; R Mangues; J R Germà; J G Herman; G Capellà; M A Peinado Journal: J Clin Oncol Date: 2001-01-15 Impact factor: 44.544
Authors: J L Bos; E R Fearon; S R Hamilton; M Verlaan-de Vries; J H van Boom; A J van der Eb; B Vogelstein Journal: Nature Date: 1987 May 28-Jun 3 Impact factor: 49.962
Authors: Carla Oliveira; Jantine L Westra; Diego Arango; Miina Ollikainen; Enric Domingo; Ana Ferreira; Sérgia Velho; Renee Niessen; Kristina Lagerstedt; Pia Alhopuro; Paivi Laiho; Isabel Veiga; Manuel R Teixeira; Marjolijn Ligtenberg; Jan H Kleibeuker; Rolf H Sijmons; John T Plukker; Kohzoh Imai; Pedro Lage; Richard Hamelin; Cristina Albuquerque; Simo Schwartz; Annika Lindblom; Päivi Peltomaki; Hiroyuki Yamamoto; Lauri A Aaltonen; Raquel Seruca; Robert M W Hofstra Journal: Hum Mol Genet Date: 2004-08-04 Impact factor: 6.150
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