Predictive Biomarkers in Colorectal Cancer: From the Single Therapeutic Target to a Plethora of Options

Rodrigues, Daniela; Longatto‐Filho, Adhemar; Martins, Sandra F.

doi:10.1155/2016/6896024

Cited by 20 publications

(16 citation statements)

References 80 publications

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“…It was recently announced that the drugs with certain mechanisms of action are targeted by molecules in tumors and are not so effective for common cancers. It was also announced that approaching a single target cannot inhibit the tumor progression in multisystem involving cancers such as colorectal cancer [ 12 ]. By analyzing these study results, it is shown that the failure or less effect of drugs may be caused by interaction of many signal pathways.…”

Section: Resultsmentioning

confidence: 99%

A cross-talk between integrin β4 and epidermal growth factor receptor induces gefitinib chemoresistance to gastric cancer

Huafeng¹,

Zhang

Yong³

et al. 2018

Cancer Cell Int

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BackgroundGastric cancer presents a major health burden worldwide. Therefore, many molecular targeting agents have been evaluated for treatment of gastric cancer. Gefitinib has shown anticancer activity against gastric cancer which work through inhibiting epidermal growth factor receptor (EGFR). However, the effect of gefitinib is limited due to its resistance. Therefore, understanding the mechanisms of gefitinib resistance is desperately needed to formulate novel strategies against gastric cancer. Here, we analyzed resistance mechanism from the crosstalk between EGFR and integrin β4.MethodsIntegrin β4-expression vector or siRNA were used to analyze the functional effects of integrin β4 on chemoresistance of gastric cancer cells to gefitinib. EGFR and integrin β4 expression, proliferation and apoptosis of gastric cancer cells were assayed by indirect immunofluorescence, western blot, MTT and flow cytometry respectively. EGFR and integrin β4 expression were also assayed on patient samples.ResultsIt was found that the integrin β4 expression was increased in gefitinib-resistant gastric cell line. The upregulated integrin β4 expression was identified to promote gefitinib resistance and proliferation, and inhibit apoptosis, while downregulation of integrin β4 was to inhibit gefitinib resistance and proliferation, and induce apoptosis. Moreover, the overexpression of integrin β4 in SGC7901 cells resulted in the down-regulation of p-EGFR protein levels while down-regulation of integrin β4, significantly resulted in overexpression of p-EGFR. The results of western blot from patients also showed there was obvious negative correlation between p-EGFR and integrin β4 in gastric cancer patients.ConclusionConsidering the above results, it is concluded that the interaction of EGFR and integrin β4 may change the sensitivity of gefitinib treatment.

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Section: Resultsmentioning

confidence: 99%

A cross-talk between integrin β4 and epidermal growth factor receptor induces gefitinib chemoresistance to gastric cancer

Huafeng¹,

Zhang

Yong³

et al. 2018

Cancer Cell Int

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“…Colorectal cancer develops from the progressive accumulation of molecular events, like somatic mutations in oncogenes, or epigenetic mechanisms such as methylation of DNA or post-transcriptional modification of histones 2 . Over recent years, various studies have focused on the discovery of the molecular changes that participate in the process of tumour development, with the aim of finding biomarkers potentially useful in predicting survival or directing therapeutic strategies 3 .…”

Section: Introductionmentioning

confidence: 99%

The role of EZH2 in overall survival of colorectal cancer: a meta-analysis

Vilorio-Marqués

Martín

Diez-Tascón³

et al. 2017

Sci Rep

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Enhancer of zeste homolog 2 (EZH2) is the catalitic subunit of polycomb repressive complex 2 and mediates gene silencing. EZH2 is overexpressed in many cancers and correlates with poor prognosis. The role of the gene EZH2 in colorectal cancer survival is uncertainly, the aim of this study is clear this relationship. Relevant literaure was searched from electronic databases. A meta-analysis was performed with elegible studies which quantitatively evaluated the relationship between EZH2 overexpression and survival of patients with colorectal cancer. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 8 studies (n = 1059 patients) that evaluated the correlation between EZH2 overexpression and survival in patients with colorectal cancer. Combined hazard ratios suggested that EZH2 overexpression was associated with better prognosis of overall survival (OS) HR(hazard ratio) = 0.61 95% CI (0.38–0.84) We performed bias analysis according Egger and Begg,s test and we did not find publication bias. EZH2 overexpression indicates a better prognosis for colorectal cancer.

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“…The significance of (KRAS) Kirsten rat sarcoma viral oncogene homolog mutational profile as a negative predictive biomarker in the treatment response of mCRC using monoclonal antibody (mAb) against epidermal growth factor receptor (EGFR) is well established [55][56][57]. Clinical trials such as PRIME (panitumumab) and CRYSTAL (cetuximab) demonstrated positive response towards anti-EGFR mAb therapies only in wild-type (WT) KRAS mCRC patients.…”

Section: Kras (Kirsten Rat Sarcoma Viral Oncogene Homolog)mentioning

confidence: 99%

“…Significant correlations with known CRC biomarkers such as MSI-H, KRAS, and BRAF mutations were also reported [100]. A simplified summary of the biomarkers reviewed in Section 2.1 to 2.4 is presented in Figure 2 [18,19,43,54,56,57,70,74,78,79,88,[91][92][93][94]96,97,[100][101][102][103][104][105].…”

Section: Consensus Molecular Subtypes (Cms)mentioning

confidence: 99%

Current Update of Laboratory Molecular Diagnostics Advancement in Management of Colorectal Cancer (CRC)

et al. 2019

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Colorectal cancer (CRC) continues to be one of the most common cancers globally. The incidence has increased in developing countries in the past few decades, this could be partly attributed to aging populations and unhealthy lifestyles. While the treatment of CRC has seen significant improvement since the advent of target-specific therapies and personalized medicine, CRC is oftentimes detected at late or advanced stages, thereby reducing the efficacy of treatment. Hence, screening for early detection is still the key to combat CRC and to increase overall survival (OS). Considering that the field of medical diagnostics is moving towards molecular diagnostics, CRC can now be effectively screened and diagnosed with high accuracy and sensitivity. Depending on the tumor genotype and genetic profile of the individual, personalized treatments including tyrosine kinase inhibitor therapy and immunotherapy can be administered. Notably, there can be no one single treatment that is effective for all CRC patients due to the variation in tumor genetics, which highlights the importance of molecular diagnostics. This review provides insights on therapeutic modalities, molecular biomarkers, advancement of diagnostic technologies, and current challenges in managing CRC.

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Predictive Biomarkers in Colorectal Cancer: From the Single Therapeutic Target to a Plethora of Options

Cited by 20 publications

References 80 publications

A cross-talk between integrin β4 and epidermal growth factor receptor induces gefitinib chemoresistance to gastric cancer

A cross-talk between integrin β4 and epidermal growth factor receptor induces gefitinib chemoresistance to gastric cancer

The role of EZH2 in overall survival of colorectal cancer: a meta-analysis

Current Update of Laboratory Molecular Diagnostics Advancement in Management of Colorectal Cancer (CRC)

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