scholarly journals Synchronous Colorectal Cancer: Improving Accuracy of Detection and Analyzing Molecular Heterogeneity—The Main Keys for Optimal Approach

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 314
Author(s):  
Patricia Simu ◽  
Ioan Jung ◽  
Laura Banias ◽  
Zsolt Kovacs ◽  
Zsolt Zoltan Fulop ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Molecular Profile ◽  
Molecular Heterogeneity ◽  
Braf Mutations ◽  
Synchronous Tumors ◽  
Mesenchymal Transition ◽  
Synchronous Colorectal Cancer ◽  
Preoperative Ct ◽  
Optimal Approach

Background: In patients with synchronous colorectal cancer (SCRC), understanding the underlying molecular behavior of such cases is mandatory for designing individualized therapy. The aim of this paper is to highlight the importance of transdisciplinary evaluation of the pre- and post-operative assessment of patients with SCRCs, from imaging to molecular investigations. Methods: Six patients with SCRCs presented with two carcinomas each. In addition to the microsatellite status (MSS), the epithelial mesenchymal transition was checked in each tumor using the biomarkers β-catenin and E-cadherin, same as KRAS and BRAF mutations. Results: In two of the patients, the second tumor was missed at endoscopy, but diagnosed by a subsequent computed-tomography-scan (CT-scan). From the six patients, a total of 11 adenocarcinomas (ADKs) and one squamous cell carcinoma (SCC) were analyzed. All the examined carcinomas were BRAF-wildtype microsatellite stable tumors with an epithelial histological subtype. In two of the six cases, KRAS gene status showed discordance between the two synchronous tumors, with mutations in the index tumors and wildtype status in the companion ones. Conclusions: Preoperative CT-scans can be useful for detection of synchronous tumors which may be missed by colonoscopy. Where synchronous tumors are identified, therapy should be based on the molecular profile of the indexed tumors.

The Evolution of Our Molecular Understanding of Colorectal Cancer: What We Are Doing Now, What the Future Holds, and How Tumor Profiling Is Just the Beginning

2014 ◽  
pp. 91-99 ◽  
Author(s):  
Rodrigo Dienstmann ◽  
Ramon Salazar ◽  
Josep Tabernero
Keyword(s):  
Colorectal Cancer ◽  
Rational Design ◽  
Cellular Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Disease Classification ◽  
Braf Mutations ◽  
Mesenchymal Transition ◽  
Molecular Features ◽  
Current Trends ◽  
Mutation Profile

Colorectal cancer (CRC) has been extensively molecularly characterized in recent years. In addition to the understanding of biologic hallmarks of the disease, the ultimate goal of these studies was to provide tools that could allow us to differentiate subgroups of CRC with prognostic and predictive implications. So far, subtype classification has been largely driven by well-described features: (1) defective mismatch repair resulting in higher mutation rate; (2) cellular proliferation along with chromosomal instability and copy number aberrations; and (3) an invasive stromal phenotype mainly driven by TGF-β linked to epithelial-mesenchymal transition. Recent studies have outlined the complexity of CRC at the gene expression level, confirming how heterogeneous the disease is beyond currently validated parameters, namely KRAS, BRAF mutations and microsatellite instability. In fact, adopting an extended mutation profile upfront, which includes nonrecurrent KRAS, NRAS, and PIK3CA gene variants, likely improves outcomes. In this article, we review the current trends of translational research in CRC, summarize ongoing genomically driven clinical trials, and describe the challenges for defining a comprehensive, robust, and reproducible disease classification system that links molecular features to personalized medicine. We believe that identification of CRC subtypes based on integrative genomic analyses will provide a better guide for patient stratification and for rational design of drugs targeting specific pathways.

scholarly journals Epithelial-Mesenchymal Transition and MicroRNAs in Colorectal Cancer Chemoresistance to FOLFOX

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 75
Author(s):  
Paula I. Escalante ◽  
Luis A. Quiñones ◽  
Héctor R. Contreras
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Methylenetetrahydrofolate Reductase ◽  
Epithelial Mesenchymal Transition ◽  
Late Onset ◽  
Dihydropyrimidine Dehydrogenase ◽  
Acquired Resistance ◽  
Potential Effect ◽  
Mesenchymal Transition ◽  
Folfox Chemotherapy

The FOLFOX scheme, based on the association of 5-fluorouracil and oxaliplatin, is the most frequently indicated chemotherapy scheme for patients diagnosed with metastatic colorectal cancer. Nevertheless, development of chemoresistance is one of the major challenges associated with this disease. It has been reported that epithelial-mesenchymal transition (EMT) is implicated in microRNA-driven modulation of tumor cells response to 5-fluorouracil and oxaliplatin. Moreover, from pharmacogenomic research, it is known that overexpression of genes encoding dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), the DNA repair enzymes ERCC1, ERCC2, and XRCC1, and the phase 2 enzyme GSTP1 impair the response to FOLFOX. It has been observed that EMT is associated with overexpression of DPYD, TYMS, ERCC1, and GSTP1. In this review, we investigated the role of miRNAs as EMT promotors in tumor cells, and its potential effect on the upregulation of DPYD, TYMS, MTHFR, ERCC1, ERCC2, XRCC1, and GSTP1 expression, which would lead to resistance of CRC tumor cells to 5-fluorouracil and oxaliplatin. This constitutes a potential mechanism of epigenetic regulation involved in late-onset of acquired resistance in mCRC patients under FOLFOX chemotherapy. Expression of these biomarker microRNAs could serve as tools for personalized medicine, and as potential therapeutic targets in the future.

B7-H4 induces epithelial–mesenchymal transition and promotes colorectal cancer stemness

2021 ◽  
pp. 153323
Author(s):  
Ying Feng ◽  
Zhaoting Yang ◽  
Chengye Zhang ◽  
Nan Che ◽  
Xingzhe Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Stemness ◽  
Mesenchymal Transition

scholarly journals The microRNA-210-Stathmin1 Axis Decreases Cell Stiffness to Facilitate the Invasiveness of Colorectal Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1833
Author(s):  
Tsai-Tsen Liao ◽  
Wei-Chung Cheng ◽  
Chih-Yung Yang ◽  
Yin-Quan Chen ◽  
Shu-Han Su ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Motility ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Stiffness ◽  
Mesenchymal Transition ◽  
Cytoskeletal Dynamics ◽  
Colorectal Cancer Stem Cells

Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

scholarly journals AKT3 Expression in Mesenchymal Colorectal Cancer Cells Drives Growth and Is Associated with Epithelial-Mesenchymal Transition

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 801
Author(s):  
Joyce Y. Buikhuisen ◽  
Patricia M. Gomez Barila ◽  
Arezo Torang ◽  
Daniëlle Dekker ◽  
Joan H. de Jong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Surrogate Marker ◽  
High Expression ◽  
Mesenchymal Transition ◽  
High Propensity ◽  
Colorectal Cancer Cells ◽  
Epithelial Compartment ◽  
Selection Of

Colorectal cancer (CRC) is a heterogeneous disease that can currently be subdivided into four distinct consensus molecular subtypes (CMS) based on gene expression profiling. The CMS4 subtype is marked by high expression of mesenchymal genes and is associated with a worse overall prognosis compared to other CMSs. Importantly, this subtype responds poorly to the standard therapies currently used to treat CRC. We set out to explore what regulatory signalling networks underlie the CMS4 phenotype of cancer cells, specifically, by analysing which kinases were more highly expressed in this subtype compared to others. We found AKT3 to be expressed in the cancer cell epithelium of CRC specimens, patient derived xenograft (PDX) models and in (primary) cell cultures representing CMS4. Importantly, chemical inhibition or knockout of this gene hampers outgrowth of this subtype, as AKT3 controls expression of the cell cycle regulator p27KIP1. Furthermore, high AKT3 expression was associated with high expression of epithelial-mesenchymal transition (EMT) genes, and this observation could be expanded to cell lines representing other carcinoma types. More importantly, this association allowed for the identification of CRC patients with a high propensity to metastasise and an associated poor prognosis. High AKT3 expression in the tumour epithelial compartment may thus be used as a surrogate marker for EMT and may allow for a selection of CRC patients that could benefit from AKT3-targeted therapy.

69. The Induction of Epithelial-Mesenchymal Transition by PTEN in Colorectal Cancer

2009 ◽  
Vol 151 (2) ◽  
pp. 202
Author(s):  
K. Bowen ◽  
B.P. Zhou ◽  
H.Q. Doan ◽  
P.G. Rychahou ◽  
B. Evers
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition
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