scholarly journals Effectiveness of circulating tumor DNA for detection of KRAS gene mutations in colorectal cancer patients: a meta-analysis

2017 ◽  
Vol Volume 10 ◽  
pp. 945-953 ◽  
Author(s):  
Yi-xin Hao ◽  
Qiang Fu ◽  
Yan-Yan Guo ◽  
Ming Ye ◽  
Hui-Xia Zhao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Gene Mutations ◽  
Circulating Tumor Dna ◽  
Kras Gene ◽  
Colorectal Cancer Patients ◽  
Tumor Dna

scholarly journals Small EVs-Associated DNA as Complementary Biomarker to Circulating Tumor DNA in Plasma of Metastatic Colorectal Cancer Patients

2021 ◽  
Vol 14 (2) ◽  
pp. 128
Author(s):  
Silvia Galbiati ◽  
Francesco Damin ◽  
Dario Brambilla ◽  
Lucia Ferraro ◽  
Nadia Soriani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Digital Pcr ◽  
Extracellular Vesicle ◽  
Circulating Tumor Dna ◽  
Mutation Status ◽  
Promising Practice ◽  
Colorectal Cancer Patients ◽  
Tumor Dna

It is widely accepted that assessing circular tumor DNA (ctDNA) in the plasma of cancer patients is a promising practice to evaluate somatic mutations from solid tumors noninvasively. Recently, it was reported that isolation of extracellular vesicles improves the detection of mutant DNA from plasma in metastatic patients; however, no consensus on the presence of dsDNA in exosomes has been reached yet. We analyzed small extracellular vesicle (sEV)-associated DNA of eleven metastatic colorectal cancer (mCRC) patients and compared the results obtained by microarray and droplet digital PCR (ddPCR) to those reported on the ctDNA fraction. We detected the same mutations found in tissue biopsies and ctDNA in all samples but, unexpectedly, in one sample, we found a KRAS mutation that was not identified either in ctDNA or tissue biopsy. Furthermore, to assess the exact location of sEV-associated DNA (outside or inside the vesicle), we treated with DNase I sEVs isolated with three different methodologies. We found that the DNA inside the vesicles is only a small fraction of that surrounding the vesicles. Its amount seems to correlate with the total amount of circulating tumor DNA. The results obtained in our experimental setting suggest that integrating ctDNA and sEV-associated DNA in mCRC patient management could provide a complete real-time assessment of the cancer mutation status.

Circulating tumor DNA to monitor treatment response and investigate resistance mechanism in BRAF inhibitor treated colorectal cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16112-e16112
Author(s):  
De-Shen Wang ◽  
Yu-Hong Li ◽  
Hua Bao ◽  
Xiaoxi Chen ◽  
Ming-Tao Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Treatment Response ◽  
Cancer Patients ◽  
Acquired Resistance ◽  
Resistance Mechanism ◽  
Braf Inhibitor ◽  
Circulating Tumor Dna ◽  
Egfr Inhibition ◽  
Colorectal Cancer Patients ◽  
Tumor Dna

e16112 Background: BRAF mutations are found in about 10% of colorectal cancer (CRC) patients and is a poor prognosis factor in standard chemotherapy. Combination of BRAF and EGFR inhibition exerts a better therapeutic effective, whereas the resistance develops through undefined mechanisms. Circulating tumor DNA (ctDNA) is a non-invasive approach to assess the genetic evolution of tumors and prognosis in response to therapy, which would help better understanding the treatment response and resistance mechanism in BRAF inhibitor treated colorectal cancer patients. Methods: We performed panel next-generation sequencing of 425 cancer-related genes in 39 serial plasma samples collect from 19 patients who have BRAF V600E mutation CRC to track the resistance during the Vemurafenib treatment in combination with Irinotecan and Cetuximab (VIC) and evaluate the treatment response. Tumor responses were assessed radiologically every two months and are used to determine patients with innate or acquired resistance Results: A total of 19 patients were enrolled into the vemurafenib treatment with irinotecan and cetuximab. By January 20, 2020, treatment had been discontinued in 12 (63.2%) of the patients due to disease progression, while the other 7 cases were still under treatment. Among them, four patients with innate resistance (n = 4, 21.1%) were defined as those with PFS of less than 2 months, while patients (n = 15, 78.9%) with acquired resistance were defined as those with PFS of greater than 2 months. The VIC regimen demonstrated efficacy in patients with BRAF-mutant mCRC, with overall response rates was 63.2% (n = 12). Changes in levels of ctDNA at 4 weeks predicts therapeutic responses. CBLB, TP53 and APC baseline mutations were enriched in baseline samples of innate resistant patients. In contrast, MYC and Cell-cycle pathway alterations were enriched in baseline samples of patients with acquired resistance. Acquired RAS and MAPK mutations, known to confer resistance to BRAF inhibitors, were identified in 60% of acquired resistance patients. Moreover, acquired TGFBR2 and SMAD4 loss-of-function mutations were identified as novel resistant mechanism to the combination of BRAF and EGFR inhibition. Experimental validation is ongoing. Conclusions: Longitudinal analysis of ctDNA in BRAF CRC patients provides insights of molecular difference between innate and acquired resistance and gene alternation during resistance requiring. Serial ctDNA monitoring provides early indication of response to BRAF inhibitor in CRC patients.

scholarly journals Minimal Residual Disease Detection using a Plasma-Only Circulating Tumor DNA Assay in Colorectal Cancer Patients

2021 ◽  
pp. clincanres.0410.2021
Author(s):  
Aparna R. Parikh ◽  
Emily E. Van Seventer ◽  
Giulia Siravegna ◽  
Anna V Hartwig ◽  
Ariel Jaimovich ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Disease Detection ◽  
Dna Assay ◽  
Colorectal Cancer Patients ◽  
Tumor Dna ◽  
Minimal Residual
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