2010
DOI: 10.1016/j.radonc.2009.10.001
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KRAS and BRAF mutations in patients with rectal cancer treated with preoperative chemoradiotherapy

Abstract: We are the first to report the mutation status of KRAS and BRAF in pre-therapeutic biopsies from locally advanced rectal cancers. The high number of KRAS mutations in codons 61 and 146 emphasizes the importance to expand current mutation analyses, whereas BRAF mutations are not relevant for rectal carcinogenesis. Although the KRAS mutation status was not correlated with response, the subtle difference between G12V and G13D mutations warrants analysis of a larger patient population.

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Cited by 90 publications
(65 citation statements)
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“…6 An analysis of 94 rectal cancer patients treated with preoperative chemoradiation therapy concluded that G12V mutations appeared to be associated with a lower rate of tumor regression than G13D mutations. 7 Similar results were noted in Dukes B and C colon cancer patients where those harboring G12V mutations had shorter disease-free and overall survival. 8 However, the emerging data on KRAS G13D mutation status and resistance to anti-EGFR therapy are inconsistent and conflicting with some studies, suggesting that the mutation confers patients with improved tumor response and progression-free survival with ant-EGFR therapy, whereas other do not.…”
supporting
confidence: 70%
“…6 An analysis of 94 rectal cancer patients treated with preoperative chemoradiation therapy concluded that G12V mutations appeared to be associated with a lower rate of tumor regression than G13D mutations. 7 Similar results were noted in Dukes B and C colon cancer patients where those harboring G12V mutations had shorter disease-free and overall survival. 8 However, the emerging data on KRAS G13D mutation status and resistance to anti-EGFR therapy are inconsistent and conflicting with some studies, suggesting that the mutation confers patients with improved tumor response and progression-free survival with ant-EGFR therapy, whereas other do not.…”
supporting
confidence: 70%
“…23 However, the impact of BRAF mutational status on response to preoperative chemoradiation is still controversial, with some studies showing low pathological complete response rates in RAS-or BRAFmutated tumors 6,7 and others no impact 8,9 and this is likely due to the small number of BRAF-mutated rectal carcinomas in these clinical series. In such a context, the question whether BRAF oncogenic mutations enhance the apoptotic threshold of rectal cancer cells and impact on response to radiation is extremely relevant, since it is established that human BRAF V600E CRCs are resistant to apoptosis and poorly responsive to standard chemotherapeutics and molecular targeted agents.…”
Section: Discussionmentioning
confidence: 99%
“…5 By contrast, conflicting results have been proposed on the role of BRAF mutations in driving the sensitivity of rectal carcinoma cells to radiation, with some studies showing poor responses and others no influence. [6][7][8][9] Thus, this study was designed to evaluate in vitro the radiosensitivity of CRC cells with different RAS/BRAF mutational profiles and exploit cyclin-dependent kinase 1 (CDK1) targeting as a strategy to improve efficacy of radiation therapy in BRAF V600E tumor cells.…”
Section: Introductionmentioning
confidence: 99%
“…Der KRAS-Status korrelierte weder mit dem Ansprechen auf die RCT noch mit dem OS. Lediglich bei G12V-Mutationen wurde, verglichen mit G13D-Mutationen, signifikant häufiger eine RCT-induzierte Tumorregression beobachtet, allerdings sind weitere Untersuchungen an größeren Patientenkollektiven erforderlich [114]. Da bei Rektumkarzinomen mit KRASMutationen bestimmte Gene, darunter DUSP4, eine MAPKinase-Phosphatase, und SMYD3, eine Histon-Methyltransferase, überexprimiert werden, besteht hier ein potenzieller Ansatzpunkt zur Entwicklung neuer, zielgerichteter Therapeutika, mit deren Hilfe die Resistenz der KRAS-mutierten Karzinome gegenüber EGFR-Antikörpern möglicherweise überwunden werden könnte [115].…”
Section: Induktionschemotherapie Vor Neoadjuvanter Rct Beim Rektumkarunclassified