Several antibodies abrogating EGFR-signaling are being used in the treatment of metastasized cancers (Cetuximab, Panitumumab)

msra

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摘要
There is a hot spot for KRAS mutations in codon 12 and 13 of the second exon. Therefore, mutational analyses are fairly easy to conduct because only a short segment of the gene needs to be analysed. This can be done in formalin-fixed, paraffin-embedded tumor samples. The samples should be enriched for tumor cells by macro- or microdissection, DNA can then be extracted and analysed using either Sanger sequencing, allele specific PCR or pyrosequencing. All three methods will be explained and illustrated with examples. An estimate of cost and working hours for all three methods will be given. As of now, there is no "gold standard" of KRAS mutational analysis. All methods can be used, but quality controls including interlaboratory tests should be conducted to ensure high quality of the methology and correct results of the mutational analyses. The experience of the German Panitumumab Advisory Board will be discussed to illustrate the use of interlaboratory tests. The KRAS mutational analyses can be conducted using the primary tumor, there is no need for a pretreatment biopsy of the metastasis since there is almost complete agreement regarding the KRAS status of primary tumor and metastasis. Data will be shown to prove that. The experience of the German Panitumumab Advisory Board will be discussed. References Editorials and Reviews about targeted therapy Wong R, Cunningham D. Using predictive biomarkers to select patients with advanced colorectal cancer for treatment with epidermal growth factor receptor antibodies. J Clin Oncol 2008; 26:5668-70
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