<i><scp>KRAS</scp></i> status and resistance to epidermal growth factor receptor tyrosine‐kinase inhibitor treatment in patients with metastatic colorectal cancer: a meta‐analysis

Li, Wenhao; Shi, Qi; Wang, W.; Liu, J.; Ren, Jianlin; Li, Q.; Hou, Fenggang

doi:10.1111/codi.12749

Cited by 11 publications

(12 citation statements)

References 31 publications

(44 reference statements)

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“…Previous studies have shown that tumors with high methylation status (called the CpG island methylation phenotype [CIMP] in previous studies) are closely associated with MSI‐high CRC . Thus, methylation status has been subclassified into two groups: CIMP‐high and CIM‐low . Although most studies have used one group of classifier markers, including original CIMP markers (the one‐panel method), Yagi and Kaneda recently used a two‐panel method and subclassified tumors into three groups: HME, IME, and LME.…”

Section: Discussionmentioning

confidence: 99%

“…This finding is relevant for the development of therapies for CRC because targeted biological agents, such as cetuximab, are influenced by KRAS mutations. (29) Therefore, tumors within this subgroup may not be affected by cetuximab therapy, a promising recent development in therapeutic options for CRC.…”

Section: Discussionmentioning

confidence: 99%

“…(31,32) Thus, methylation status has been subclassified into two groups: CIMP-high and CIM-low. (29,33) Although most studies have used one group of classifier markers, (31,32) including original CIMP markers (the one-panel method), Yagi and Kaneda recently used a two-panel method (22,23) and subclassified tumors into three groups: HME, IME, and LME. According to their study, HME is strongly correlated with MSI-high status and BRAF mutations in CRC, which is consistent with previous studies in which the one-panel method was used.…”

Section: Discussionmentioning

confidence: 99%

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Molecular subtypes of colorectal cancers determined by PCR‐based analysis

et al. 2017

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Tumor tissue consists of a heterogeneous cell population. The allelic imbalance (AI) ratio, determined in isolated tumor glands, is a good index of tumor heterogeneity. However, associations of the patterns of AI and microsatellite instability (MSI) development, observed in most cases of colorectal cancer (CRC), with tumor progression have not been reported previously. In this study, we examined whether CRC genetic profiles stratified by a combination of the AI ratio and MSI facilitate categorization of CRC, and whether these genetic profiles are associated with specific molecular alterations in CRC. A crypt isolation method was used to isolate DNA from tumors and normal glands obtained from 147 sporadic CRCs. AI and MSI statuses were determined using PCR‐based microsatellite analysis and stratified based on AI ratio and MSI status. DNA methylation status (high methylation, intermediate methylation and low methylation status and mutations in KRAS,BRAF, and TP53 were examined. In addition, mucin markers were immunostained. Based on this analysis, four subgroups were categorized. Subgroup 1 was characterized by a high MSI status and BRAF mutation; subgroup 2 was closely associated with a high AI ratio, which accumulated during the early phases of colorectal carcinogenesis, and TP53 mutation; subgroup 3 was associated with a low AI ratio, seen during the later phases of colorectal carcinogenesis, and KRAS mutation; and subgroup 4 was defined as a minor subgroup. These results confirmed that classification of distinct molecular profiles provides important insights into colorectal carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Molecular subtypes of colorectal cancers determined by PCR‐based analysis

et al. 2017

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“…RAS and RAF gene mutations have been considered potential markers of sensitivity to MEK inhibition largely due to the constitutive activation of MEK seen in BRAF mutant cancer cells and to a lesser extent in KRAS mutant cells [ 17 , 18 ]. Thus, MEK has become a potential target for therapy given that mutation in these kinases has been identified as a negative predictor of benefit from EGFR inhibitor therapy [ 19 , 20 , 21 ]. However, acquired resistance after MEK inhibition seems inevitable.…”

Section: Cross-talk Between Mek and Pi3k Pathwaymentioning

confidence: 99%

Dual Inhibition of MEK and PI3K Pathway in KRAS and BRAF Mutated Colorectal Cancers

Temraz

Mukherji

Shamseddine

2015

IJMS

101

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Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. Genetic mutations in the phosphatidylinositol-3 kinase (PI3K) and the mitogen activated protein kinase (MAPK) pathways are frequently implicated in CRC. Targeting the downstream substrate MEK in these mutated tumors stands out as a potential target in CRC. Several selective inhibitors of MEK have entered clinical trial evaluation; however, clinical activity with single MEK inhibitors has been rarely observed and acquired resistance seems to be inevitable. Amplification of the driving oncogene KRAS(13D), which increases signaling through the ERK1/2 pathway, upregulation of the noncanonical wingless/calcium signaling pathway (Wnt), and coexisting PIK3CA mutations have all been implicated with resistance against MEK inhibitor therapy in KRAS mutated CRC. The Wnt pathway and amplification of the oncogene have also been associated with resistance to MEK inhibitors in CRCs harboring BRAF mutations. Thus, dual targeted inhibition of MEK and PI3K pathway effectors (mTOR, PI3K, AKT, IGF-1R or PI3K/mTOR inhibitors) presents a potential strategy to overcome resistance to MEK inhibitor therapy. Many clinical trials are underway to evaluate multiple combinations of these pathway inhibitors in solid tumors.

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“…The RAS protein exhibits intrinsic guanosine triphosphate (GTP) enzymatic activity, and is involved in cell proliferation, differentiation, and apoptosis by switching the mutual transformation regulatory signal system between guanosine diphosphate (GDP) and GTP. The KRAS gene has a high mutation rate in patients with colorectal cancer and lung cancer, and confers the resistance to epidermal growth factor receptor (EGFR), tyrosine kinase inhibitors (TKIs), and EGFR monoclonal antibody agents ( Chen et al , 2013 ; Li et al , 2014 ; Leiser et al , 2015 ; Hsu et al , 2016 ). Reports indicate that KRAS gene mutations in patients with non-small cell lung cancer are related to short survival time and poor prognosis ( Li et al , 2016 ; Tao et al , 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Performance of probe polymerization-conjunction-agarose gel electrophoresis in the rapid detection of KRAS gene mutation

Xiao

Tang

et al. 2018

Genet. Mol. Biol.

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This study aimed to develop a simple and rapid method to detect KRAS gene mutations for conventional clinical applications under laboratory conditions. The genotype of mutation sites was determined based on the occurrence of target bands in the corresponding lanes of the reaction tubes through polymerization-conjunction of the probes, probe purification and amplification, and agarose gel electrophoresis. Circulating DNA samples were obtained from the plasma of 72 patients with lung cancer, which were identified based on six mutation sites (G12S, G12R, G12C, G12D, G12A, and G12V) of codon 12 of the KRAS gene. The detection results were compared with direct sequencing data. The proposed detection method is characterized by simple operation, high specificity, and high sensitivity (2%). This method can detect the mutations of three samples at G12S, G12R, and G12A. In the direct sequencing spectra of these samples, the genotype could not be determined due to the lack of evident sequencing peaks that correspond to the basic group of mutations. In conclusion, a simple and rapid method was established based on probe polymerization-conjunction-agarose gel electrophoresis for detecting KRAS gene mutations. This method can be applied to the conventional mutation detection of inhomogeneous samples.

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KRAS status and resistance to epidermal growth factor receptor tyrosine‐kinase inhibitor treatment in patients with metastatic colorectal cancer: a meta‐analysis

Abstract: All the results favoured a stronger link between mutant KRAS and anti-EGFR mAb, but due to a mutually exclusive relationship between KRAS and other gene mutations the clinical usefulness of KRAS mutation as a selection marker for sensitivity to EGFR TKIs in mCRC is limited.

Cited by 11 publications

References 31 publications

Molecular subtypes of colorectal cancers determined by PCR‐based analysis

Molecular subtypes of colorectal cancers determined by PCR‐based analysis

Dual Inhibition of MEK and PI3K Pathway in KRAS and BRAF Mutated Colorectal Cancers

Performance of probe polymerization-conjunction-agarose gel electrophoresis in the rapid detection of KRAS gene mutation

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