Quantitative Cell-Free DNA, <i>KRAS</i>, and <i>BRAF</i> Mutations in Plasma from Patients with Metastatic Colorectal Cancer during Treatment with Cetuximab and Irinotecan

Spindler, Karen‐Lise Garm; Pallisgaard, Niels; Vogelius, I.R.; Jakobsen, Anders

doi:10.1158/1078-0432.ccr-11-0564

Cited by 242 publications

(239 citation statements)

References 24 publications

(29 reference statements)

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“…A higher incidence of plasma KRAS mutation was associated with a lower survival rate in colorectal cancer and non-small cell lung cancer (41). Higher levels of plasma KRAS mutation were also correlated with poor tumor control with treatment of cetuximab and irinotecan (42). However, the relationship between tumor regression response induced by preoperative chemoradiotherapy and the incidence of KRAS mutation in baseline plasma DNA was not found.…”

Section: Discussionmentioning

confidence: 96%

The role of plasma cell-free DNA detection in predicting preoperative chemoradiotherapy response in rectal cancer patients

Sun

Zhu

et al. 2013

Oncology Reports

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Abstract. In the present study, we studied the relationship between plasma cell-free DNA and the effect of preoperative chemoradiotherapy in patients with rectal cancer. The concentration, KRAS mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status of cell-free DNA were measured by using polymerase chain reaction (PCR) analyses. The response to chemoradiotherapy was assessed using tumor regression grading (TRG) scores. The cell-free DNA concentrations in patients with rectal cancer (n=34) were significantly higher compared to healthy controls (n=10). The 400-base pair (bp) DNA concentration, 400-/100-bp DNA ratio decreased significantly after chemoradiotherapy in the good response group. The incidence of KRAS mutation decreased significantly after chemoradiotherapy in both good and poor response groups. Higher MGMT promoter methylation status at baseline DNA was associated with a better tumor response. Therefore, cell-free DNA detection may be useful in evaluating the effect of preoperative chemoradiotherapy in patients with rectal cancer.

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Section: Discussionmentioning

confidence: 96%

The role of plasma cell-free DNA detection in predicting preoperative chemoradiotherapy response in rectal cancer patients

Sun

Zhu

et al. 2013

Oncology Reports

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“…However, the relationship between mutation detection and treatment efficacy has not yet been elucidated. According to a recent report, quantity of KRAS mutations in plasma was significantly correlated with efficacy of chemotherapy using cetuximab and irinotecan [26]. A higher level of mutated KRAS in plasma detected by quantitative PCR corresponded with a lower disease control rate (DCR); patients with greater than the upper quartile (75%) of KRAS mutation level had a DCR of 0%, whereas those with less than the upper quartile had a DCR of 42%.…”

Section: Discussionmentioning

confidence: 99%

Detection of KRAS Mutations in Plasma DNA Using a fully Automated Rapid Detection System in Colorectal Cancer Patients

Hosoya

Matsusaka

Kashiwada

et al. 2017

Pathol. Oncol. Res.

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KRAS mutations have been recognized as predictive markers of primary resistance to anti-EGFR-antibodies in colorectal cancer patients. In addition, newly detected KRAS mutations have been reported to be related with acquired resistance to chemotherapy containing anti-EGFR antibody. Considering this evidence, monitoring of KRAS mutations is indispensable for making treatment decisions, and the method should be non-invasive allowing repeated examinations. Recently, we established a novel automated sensitive detection system for KRAS mutations, named mutation-biased PCR quenching probe system (MBP-QP). The goal of our study was to investigate the potential for monitoring KRAS mutations during treatment with anti-EGFR antibodies. The detection limit of MBP-QP using a control plasmid containing KRAS mutations was 1-9 copies, and 0.05-0.3% mutant plasmid was detectable in a mixture of wild type and mutants. One-hundred twenty colorectal cancer patients were genotyped for KRAS mutations with MBP-QP as well as polymerase chain reaction reverse sequence-specific oligonucleotide (PCR-rSSO), which has already been applied to cancer tissue samples in the clinical setting. Concordance rates between plasma DNA and cancer tissues were 68% with MBP-QP and 66% with PCR-rSSO, indicating that these systems are equivalent in terms of detecting KRAS mutations with plasma DNA. KRAS mutations in plasma DNA were frequently observed in systemic metastatic cancer patients, and in three patients KRAS mutations appeared after chemotherapy containing anti-EGFR antibody. A prospective study is needed for clarifying whether KRAS mutations detected in plasma DNA are predictive markers of treatment efficacy with anti-EGFR antibody.

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“…Spindler et al used quantitative PCR method to assess the number of cfDNA alleles, as well as Kirsten rat sarcoma viral oncogene homolog (KRAS) and BRAF mutation alleles, in plasma from patients with metastatic colorectal cancer (mCRC) undergoing treatment with cetuximab and irinotecan. The majority of KRAS mutations detected in tumors were also found in the plasma, and cox analysis confirmed the prognostic importance of both cfDNA and pmKRAS (Spindler et al, 2012). Taly et al investigated using multiplex picodroplet digital PCR (dPCR) to screen for the most common mutations in codons of the KRAS oncogene in the plasma of patients with metastatic colorectal cancer.…”

Section: Liquid Biopsies In Tumour Diagnosis and Treatmentmentioning

confidence: 99%

Liquid biopsies: tumour diagnosis and treatment monitoring

Pham

2016

Biomed Res Ther

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Abstract-Cancer is a disease with high evolutionary, i.e., malignant, characteristics that change under selective pressure from therapy. Characterization based on molecular or primary tumor properties or clinicopathological staging does not fully reflect the state of cancer, especially when cancer cells metastasize. This is the major reason for failure of cancer treatment. Currently, there is an urgent need for new approaches that allow more effective, but less invasive, monitoring of cancer status, thereby improving the efficacy of treatments. With recent technological advances, "liquid biopsies," the isolation of intact cells or analysis of components that are secreted from cells, such as nucleic acids or exosomes, could be implemented easily. This approach would facilitate real-time monitoring and accurate measurement of critical biomarkers. In this review, we summarize the recent progress in the identification of circulating tumor cells using new high-resolution approaches and discuss new circulating tumor nucleic acid-and exosome-based approaches. The information obtained through liquid biopsies could be used to gain a better understanding of cancer cell invasiveness and metastatic competence, which would then benefit translational applications such as personalized medicine.

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Quantitative Cell-Free DNA, KRAS, and BRAF Mutations in Plasma from Patients with Metastatic Colorectal Cancer during Treatment with Cetuximab and Irinotecan

Cited by 242 publications

References 24 publications

The role of plasma cell-free DNA detection in predicting preoperative chemoradiotherapy response in rectal cancer patients

The role of plasma cell-free DNA detection in predicting preoperative chemoradiotherapy response in rectal cancer patients

Detection of KRAS Mutations in Plasma DNA Using a fully Automated Rapid Detection System in Colorectal Cancer Patients

Liquid biopsies: tumour diagnosis and treatment monitoring

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