Heterogeneity in the colorectal primary tumor and the synchronous resected liver metastases prior to and after treatment with an anti-EGFR monoclonal antibody

Adua, Daniela; Fabio, Francesca Di; Ercolani, Giorgio; Fiorentino, Michelangelo; Gruppioni, Elisa; Altimari, Annalisa; Limpe, Fabiola Lorena Rojas; Normanno, Nicola; Pinna, Antonio Daniele; Pinto, Carmine

doi:10.3892/mco.2017.1270

Cited by 16 publications

(14 citation statements)

References 22 publications

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“…Other studies have confirmed the consistent heterogeneity of colorectal cancers at the level of primary tumors and synchronous metastases: this heterogeneity was present before and after anti-EGFR therapy [ 229 ]. Particularly, mutations were observed during therapy loss and the acquisition of KRAS , NRAS , TP53 , PIK3CA , FBXW7 and PTEN [ 230 ].…”

Section: Somatic Genetic Abnormalities In Colon Cancermentioning

confidence: 99%

Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells

2018

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Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20–30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian inheritance syndrome. In many patients, the development of a colorectal cancer is preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated polyp. Studies carried out in the last years have characterized the main molecular alterations occurring in colorectal cancers, showing that the tumor of each patient displays from two to eight driver mutations. The ensemble of molecular studies, including gene expression studies, has led to two proposed classifications of colorectal cancers, with the identification of four/five non-overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium is ensured by few stem cells present at the level of the base of intestinal crypts. Various experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant transformation. Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse.

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Section: Somatic Genetic Abnormalities In Colon Cancermentioning

confidence: 99%

Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells

2018

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“…Yet, another study that was conducted by Li et al (54) demonstrated that miR-223/FBXW7 axis regulates doxorubicin sensitivity through epithelial mesenchymal transition in non-small cell lung cancer. miR-223/FBXW7 pathway has also been investigated for drug resistance in cancers (38,(55)(56)(57). FBXW7 mutation drives acquired resistance to targeted agents cetuximab or panitumumab (58).…”

Section: F-box Proteins and Chemoresistancementioning

confidence: 99%

F‑box proteins involved in cancer‑associated drug resistance (Review)

et al. 2018

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The ubiquitin proteasome system (UPS) regulated human biological processes through the appropriate and efficient proteolysis of cellular proteins. F-box proteins are the vital components of SKP1-CUL1-FBP (SCF)-type E3 ubiquitin ligases that determine substrate specificity. As F-box proteins have the ability to control the degradation of several crucial protein targets associated with drug resistance, the dysregulation of these proteins may lead to induction of chemoresistance in cancer cells. Chemotherapy is one of the most conventional therapeutic approaches of treatment of patients with cancer. However, its exclusive application in clinical settings is restricted due to the development of chemoresistance, which typically results treatment failure. Therefore, overcoming drug resistance is considered as one of the most critical issues that researchers and clinician associated with oncology face. The present review serves to provide a comprehensive overview of F-box proteins and their possible targets as well as their correlation with the chemoresistance and chemosensitization of cancer cells. The article also presents an integrated representation of the complex regulatory mechanisms responsible for chemoresistance, which may lay the foundation to explore sensible candidate drugs for therapeutic intervention.

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“…Adua et al analyzed primary tumor and liver metastasis samples from 7 KRAS wild‐type patients and compared the genotypes of 22 genes associated with anti‐EGFR before and after chemotherapy. The results showed marked genotypic differences between pre‐ and post‐treatment samples, which were likely attributable to tumor cell clones selected by therapy . Gong et al analyzed 315 cancer‐related genes and introns of 28 frequently rearranged genes in 138 mCRC cases using FoundationOne.…”

Section: Introductionmentioning

confidence: 99%

“…The results showed marked genotypic differences between pre-and post-treatment samples, which were likely attributable to tumor cell clones selected by therapy. 9 Gong et al analyzed 315 cancer-related genes and introns of 28 frequently rearranged genes in 138 mCRC cases using FoundationOne. They identified a novel KRAS mutation (R68S) associated with an aggressive phenotype.…”

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confidence: 99%

Molecular characterization of colorectal cancer using whole‐exome sequencing in a Taiwanese population

et al. 2019

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Next‐generation sequencing (NGS) technology is currently used to establish mutational profiles in many heterogeneous diseases. The aim of this study was to evaluate the mutational spectrum in Taiwanese patients with colorectal cancer (CRC) to help clinicians identify the best treatment method. Whole‐exome sequencing was conducted in 32 surgical tumor tissues from patients with CRC. DNA libraries were generated using the Illumina TruSeq DNA Exome, and sequencing was performed on the Illumina NextSeq 500 system. Variants were annotated and compared to those obtained from publicly available databases. The analysis revealed frequent mutations in APC (59.38%), TP53 (50%), RAS (28.13%), FBXW7 (18.75%), RAF (9.38%), PIK3CA (9.38%), SMAD4 (9.38%), and SOX9 (9.38%). A mutation in TCF7L2 was also detected, but at lower frequencies. Two or more mutations were found in 22 (68.75%) samples. The mutation rates for the WNT, P53, RTK‐RAS, TGF‐β, and PI3K pathways were 78.13%, 56.25%, 40.63%, 18.75%, and 15.63%, respectively. RTK‐RAS pathway mutations were correlated with tumor size ( P = 0.028). We also discovered 23 novel mutations in NRAS , PIK3CA , SOX9 , APC , SMAD4 , MSH3 , MSH4 , PMS1 PMS2 , AXIN2 , ERBB2 , PIK3R1 , TGFBR2 , and ATM that were not reported in the COSMIC, The Cancer Genome Atlas, and dbSNP databases. In summary, we report the mutational landscape of CRC in a Taiwanese population. NGS is a cost‐effective and time‐saving method, and we believe that NGS will help clinicians to treat CRC patients in the near future.

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Heterogeneity in the colorectal primary tumor and the synchronous resected liver metastases prior to and after treatment with an anti-EGFR monoclonal antibody

Cited by 16 publications

References 22 publications

Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells

Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells

F‑box proteins involved in cancer‑associated drug resistance (Review)

Molecular characterization of colorectal cancer using whole‐exome sequencing in a Taiwanese population

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