scholarly journals Concordance ofKRAS/BRAFMutation Status in Metastatic Colorectal Cancer before and after Anti-EGFR Therapy

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
S. Gattenlöhner ◽  
B. Etschmann ◽  
V. Kunzmann ◽  
A. Thalheimer ◽  
M. Hack ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Targeted Therapy ◽  
Metastatic Colorectal Cancer ◽  
Kinase Inhibitors ◽  
Standard Procedure ◽  
Poor Response ◽  
Genetic Alterations ◽  
Primary Tumors ◽  
Mutation Status ◽  
Before And After

Anti-EGFR targeted therapy is a potent strategy in the treatment of metastatic colorectal cancer (mCRC) but activating mutations in theKRASgene are associated with poor response to this treatment. Therefore,KRASmutation analysis is employed in the selection of patients for EGFR-targeted therapy and various studies have shown a high concordance between the mutation status in primary CRC and corresponding metastases. However, although development of therapy related resistance occurs also in the context of novel drugs such as tyrosine kinase-inhibitors the effect of the anti-EGFR treatment on theKRAS/BRAFmutation status itself in recurrent mCRC has not yet been clarified. Therefore, we analyzed 21 mCRCs before/after anti-EGFR therapy and found a pre-/posttherapeutic concordance of theKRAS/BRAFmutation status in 20 of the 21 cases examined. In the one discordant case, further analyses revealed that a tumor mosaicism or multiple primary tumors were present, indicating that anti-EGFR therapy has no influence onKRAS/BRAFmutation status in mCRC. Moreover, as the preselection of patients with aKRASwtgenotype for anti-EGFR therapy has become a standard procedure, sample sets such ours might be the basis for future studies addressing the identification of potential anti-EGFR therapy induced genetic alterations apart fromKRAS/BRAFmutations.

scholarly journals Comparison of Kras Mutation Status Between Primary Tumors and Circulating Tumor Cells in Patients with Metastatic Colorectal Cancer (MCRC)

2013 ◽  
Vol 24 ◽  
pp. iv25
Author(s):  
Aristea Kalikaki ◽  
Helen Politaki ◽  
Maria Tzardi ◽  
Elisavet Papadimitraki ◽  
Demitris Mavroudis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Kras Mutation ◽  
Primary Tumors ◽  
Mutation Status ◽  
Kras Mutation Status

scholarly journals Mutational profiles of metastatic colorectal cancer treated with FOLFIRI plus cetuximab or bevacizumab before and after secondary resection ( AIO KRK 0306; FIRE ‐3)

2021 ◽  
Author(s):  
Arndt Stahler ◽  
Volker Heinemann ◽  
Julian Walter Holch ◽  
Jobst Christian von Einem ◽  
Christoph Benedikt Westphalen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Secondary Resection ◽  
Before And After

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.

scholarly journals Therapeutic Targeting of the Tumour Microenvironment in Metastatic Colorectal Cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 2067
Author(s):  
Rhynelle S. Dmello ◽  
Sarah Q. To ◽  
Ashwini L. Chand
Keyword(s):  
Colorectal Cancer ◽  
Targeted Therapy ◽  
Liver Metastasis ◽  
Metastatic Colorectal Cancer ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Cellular Interactions ◽  
Circulating Tumour Cells ◽  
Therapeutic Targeting ◽  
Colorectal Cancer Patients

Liver metastasis is the primary contributor to the death of patients with colorectal cancer. Despite the overall success of current treatments including targeted therapy, chemotherapy, and immunotherapy combinations in colorectal cancer patients, the prognosis of patients with liver metastasis remains poor. Recent studies have highlighted the importance of the tumour microenvironment and the crosstalk within that determines the fate of circulating tumour cells in distant organs. Understanding the interactions between liver resident cells and tumour cells colonising the liver opens new therapeutic windows for the successful treatment of metastatic colorectal cancer. Here we discuss critical cellular interactions within the tumour microenvironment in primary tumours and in liver metastases that highlight potential therapeutic targets. We also discuss recent therapeutic advances for the treatment of metastatic colorectal cancer.

scholarly journals Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
R.-D. Hofheinz ◽  
U. Ronellenfitsch ◽  
S. Kubicka ◽  
A. Falcone ◽  
I. Burkholder ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Optimal Sequence ◽  
Primary Endpoints ◽  
Disease Stabilization ◽  
Antiangiogenic Drugs ◽  
The Impact

Background. In metastatic colorectal cancer (mCRC), continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis.Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the impact of continuing antiangiogenic drugs (i) in subgroups, (ii) in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors), and (iii) on remission rates and prevention of progression.Results. Eight studies (3,668 patients) were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55–0.75) and OS (HR 0.83; 95%-CI, 0.76–0.89). PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41–3.58).Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs.

scholarly journals Discordance of KRAS Mutational Status between Primary Tumors and Liver Metastases in Colorectal Cancer: Impact on Long-Term Survival Following Radical Resection

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2148
Author(s):  
Francesco Ardito ◽  
Francesco Razionale ◽  
Lisa Salvatore ◽  
Tonia Cenci ◽  
Maria Vellone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Colorectal Tumor ◽  
Term Survival ◽  
Primary Tumors ◽  
Mutation Status ◽  
Primary Colorectal Tumor ◽  
Kras Mutation Status

If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses (p = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS (p < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; p = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

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