5,930 results match your criteria Colorectal Cancer and KRAS

miRNAs as cornerstones in colorectal cancer pathogenesis and resistance to therapy: A spotlight on signaling pathways interplay - A review.

Int J Biol Macromol 2022 Jun 26. Epub 2022 Jun 26.

Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt. Electronic address:

Colorectal cancer (CRC) is the world's third most prevalent cancer and the main cause of cancer-related mortality. A lot of work has been put into improving CRC patients' clinical care, including the development of more effective methods and wide biomarkers variety for prognostic, and diagnostic purposes. MicroRNAs (miRNAs) regulate a variety of cellular processes and play a significant role in the CRC progression and spread via controlling their target gene expression by translation inhibition or mRNA degradation. Read More

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Prognostic and Predictive Value of PIK3CA Mutations in Metastatic Colorectal Cancer.

Target Oncol 2022 Jun 29. Epub 2022 Jun 29.

Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA.

Background: Comprehensive genomic profiling is used to guide the management of metastatic colorectal cancer (mCRC); however, the role of PIK3CA mutations, present in up to 20% of mCRCs, is unclear.

Objective: This study aimed to evaluate the association of PIK3CA mutations with other common mutations in mCRC and determine the prognostic and predictive value of PIK3CA mutations.

Patients And Methods: A retrospective chart review was performed on patients in the Moffitt Clinical Genomic Database with mCRC. Read More

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Development of an Accessible Gene Expression Bioinformatics Pipeline to Study Driver Mutations of Colorectal Cancer.

Altern Lab Anim 2022 Jun 28:2611929221107546. Epub 2022 Jun 28.

Strathclyde Institute of Pharmacy and Biomedical Sciences, 3527University of Strathclyde, Glasgow, UK.

Colorectal cancer (CRC) is a global cause of cancer-related mortality driven by genetic and environmental factors which influence therapeutic outcomes. The emergence of next-generation sequencing technologies enables the rapid and extensive collection and curation of genetic data for each cancer type into clinical gene expression biobanks. We report the application of bioinformatics tools for investigating the expression patterns and prognostic significance of three genes that are commonly dysregulated in colon cancer: adenomatous polyposis coli (); B-Raf proto-oncogene (); and Kirsten rat sarcoma viral oncogene homologue (). Read More

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Somatic targeted mutation profiling of colorectal cancer precursor lesions.

BMC Med Genomics 2022 Jun 28;15(1):143. Epub 2022 Jun 28.

Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Vilela, 1331, Barretos, SP, 14784-400, Brazil.

Background: Most colorectal cancers (CRC) arise from precursor lesions. This study aimed to characterize the mutation profile of colorectal cancer precursor lesions in a Brazilian population.

Methods: In total, 90 formalin-fixed paraffin-embedded colorectal precursor lesions, including 67 adenomas, 7 sessile serrated lesions, and 16 hyperplastic polyps, were analyzed by next-generation sequencing using a panel of 50 oncogenes and tumor suppressor genes. Read More

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Western-style Diet, pks Island-Carrying Escherichia coli, and Colorectal Cancer: Analyses from Two Large Prospective Cohort Studies.

Gastroenterology 2022 Jun 23. Epub 2022 Jun 23.

Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Background And Aims: Evidence supports a carcinogenic role of Escherichia coli carrying the polyketide synthase (pks) island that encodes enzymes for colibactin biosynthesis. We hypothesized that the association of western-style diet (rich in red and processed meat) with colorectal cancer incidence might be stronger for tumors containing higher amounts of pks+ E. coli. Read More

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The impact of molecular and mismatch repair status on the survival outcomes of surgically treated patients with colorectal peritoneal metastases.

Eur J Surg Oncol 2022 Jun 18. Epub 2022 Jun 18.

Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia; Peter MacCallum Cancer Centre, Division of Medical Oncology, Australia.

Background: Stratification of patients with colorectal peritoneal metastases (CRPM) using RAS/BRAF mutational status may refine patient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This study aimed to analyse the association of RAS/BRAF status and their variants, with clinicopathological variables and survival outcomes in patients who have undergone CRS ± HIPEC.

Methods: A single centre, peritonectomy database was interrogated for patients with CRPM who underwent peritonectomy procedures between 2010 and 2020. Read More

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Molecular mechanisms underlying the resistance of BRAF V600E-mutant metastatic colorectal cancer to EGFR/BRAF inhibitors.

Ther Adv Med Oncol 2022 16;14:17588359221105022. Epub 2022 Jun 16.

Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China.

Background: Combinatorial inhibition of epidermal growth factor receptor (EGFR) and BRAF shows remarkable clinical benefits in patients with V600E-mutant metastatic colorectal cancer (mCRC). However, the tumor may inevitably develop resistance to the targeted therapy, thereby limiting the response rate and durability. This study aimed to determine the genetic alterations associated with intrinsic and acquired resistance to EGFR/BRAF inhibitors in V600E-mutant mCRC. Read More

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A Fraction of CD8+ T Cells from Colorectal Liver Metastases Preferentially Repopulate Autologous Patient-Derived Xenograft Tumors as Tissue-Resident Memory T Cells.

Cancers (Basel) 2022 Jun 10;14(12). Epub 2022 Jun 10.

Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.

The diversity of T cells in the human liver may reflect the composition of TILs in CRLM. Our ex vivo characterization of CRLM vs. adjacent liver tissue detected CD103+CD39+CD8+ T cells predominantly in CRLM, which prompted further assessments. Read More

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A Phase I Clinical Trial of Trametinib in Combination with TAS-102 in Patients with Chemotherapy-Resistant RAS-Mutated (PIK3CA/PTEN-Wild Type) Metastatic Colorectal Cancer.

Clin Colorectal Cancer 2022 May 23. Epub 2022 May 23.

Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA. Electronic address:

Purpose: We conducted a phase I study to evaluate the maximum tolerated dose (MTD), safety, and efficacy of trametinib in combination with TAS-102 in patients with chemotherapy-refractory KRAS-mutant, wild-type PIK3CA/PTEN metastatic colorectal cancer (mCRC).

Methods: A 3+3 dose de-escalation single arm phase I clinical trial was performed in patients with chemorefractory mCRC without priorTAS-102 exposure. Patients received fixed dosing of trametinib 2mg oral daily along with de-escalating doses of TAS-102 beginning at 35 mg/m twice daily on days 1-5 and days 8-12 every 28 days. Read More

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KRAS Gene Copy Number as a Negative Predictive Biomarker for the Treatment of Metastatic Rectal Cancer With Cetuximab: A Case Report.

Front Oncol 2022 26;12:872630. Epub 2022 May 26.

Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China.

Background: Close to one third of colorectal cancer (CRC) patients are diagnosed with metastatic CRC (mCRC). Patients with wild-type RAS and BRAF usually receive anti-EGFR monoclonal antibody therapy containing cetuximab. Overall, 30-50% of mCRC patients are reported to harbor RAS mutations, and RAS mutation status should be assessed when considering EGFR inhibitor treatment according to mCRC biomarker guidelines. Read More

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KRAS-independent feedback activation of wild-type RAS constrains KRAS inhibitor efficacy.

Cell Rep 2022 Jun;39(12):110993

Massachusetts General Hospital Cancer Center, 149 13(th) Street, 7(th) Floor, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA. Electronic address:

Although KRAS has long been considered undruggable, direct KRAS inhibitors have shown promising initial clinical efficacy. However, the majority of patients still fail to respond. Adaptive feedback reactivation of RAS-mitogen-activated protein kinase (MAPK) signaling has been proposed by our group and others as a key mediator of resistance, but the exact mechanism driving reactivation and the therapeutic implications are unclear. Read More

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Clinical and Genomic Characterization of Bladder Carcinomas With Glandular Phenotype.

JCO Precis Oncol 2022 Jun;6:e2100392

Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Purpose: To compare oncologic outcomes and genomic alteration profiles in patients with bladder and urachal adenocarcinoma, urothelial carcinoma (UC) with glandular differentiation, and UC, not otherwise specified (NOS) undergoing surgical resection, with emphasis on response to systemic therapy.

Methods: We identified patients with bladder cancer with glandular variants who underwent surgical resection at Memorial Sloan Kettering from 1995 to 2018 (surgical cohort) and/or patients who had tumor sequencing using a targeted next-generation sequencing platform (genomics cohort). Pathologic complete and partial response rates to neoadjuvant chemotherapy (NAC) and recurrence-free and cancer-specific survival were measured. Read More

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A comprehensive analysis of the microbiota composition and host driver gene mutations in colorectal cancer.

Invest New Drugs 2022 Jun 21. Epub 2022 Jun 21.

Hangzhou D.A. Medical Laboratory, Hangzhou, 310030, China.

Studies of both, microbiota and target therapy associated with gene mutations in colorectal cancer, (CRC) have attracted increasing attention. However, only a few of them analyzed the combined effects on CRC. we analyzed differences in intestinal microbiota of 44 colorectal cancer patients and 20 healthy controls (HC) using 16S rRNA gene sequencing of fecal samples. Read More

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Comparison of Next-Generation Sequencing and Polymerase Chain Reaction for Personalized Treatment-Related Genomic Status in Patients with Metastatic Colorectal Cancer.

Curr Issues Mol Biol 2022 Apr 5;44(4):1552-1563. Epub 2022 Apr 5.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.

Personalized treatments based on the genetic profiles of tumors can simultaneously optimize efficacy and minimize toxicity, which is beneficial for improving patient outcomes. This study aimed to integrate gene alterations associated with predictive and prognostic outcomes in patients with metastatic colorectal cancer (mCRC) with polymerase chain reaction (PCR) and in-house next-generation sequencing (NGS) to detect , , and mutations. In the present study, 41 patients with mCRC were assessed between August 2017 and June 2019 at a single institution. Read More

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Multigene Panel Sequencing Reveals Cancer-Specific and Common Somatic Mutations in Colorectal Cancer Patients: An Egyptian Experience.

Curr Issues Mol Biol 2022 Mar 18;44(3):1332-1352. Epub 2022 Mar 18.

Cancer Biology Department, National Cancer Institute, Cairo University, Cairo 11796, Egypt.

This study aims at identifying common pathogenic somatic mutations at different stages of colorectal carcinogenesis in Egyptian patients. Our cohort included colonoscopic biopsies collected from 120 patients: 20 biopsies from patients with inflammatory bowel disease, 38 from colonic polyp patients, and 62 from patients with colorectal cancer. On top of this, the cohort included 20 biopsies from patients with non-specific mild to moderated colitis. Read More

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Fibroblast-Induced Paradoxical PI3K Pathway Activation in PTEN-Competent Colorectal Cancer: Implications for Therapeutic PI3K/mTOR Inhibition.

Front Oncol 2022 3;12:862806. Epub 2022 Jun 3.

Section of Oncology, Department of Medicine, University of Verona School of Medicine and Verona University Hospital Trust, Verona, Italy.

Purpose: Tumor-microenvironment interactions are important determinants of drug resistance in colorectal cancer (CRC). We, therefore, set out to understand how interactions between genetically characterized CRC cells and stromal fibroblasts might influence response to molecularly targeted inhibitors.

Techniques: Sensitivity to PI3K/AKT/mTOR pathway inhibitors of CRC cell lines, with known genetic background, was investigated under different culture conditions [serum-free medium, fibroblasts' conditioned medium (CM), direct co-culture]. Read More

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Spend less to achieve more: Economic analysis of intermittent versus continuous cetuximab in KRAS wild-type patients with metastatic colorectal cancer.

J Cancer Policy 2022 Jun 16:100342. Epub 2022 Jun 16.

Patrick G Johnston Centre for Cancer Research.

Background: In 2014, the COIN-B clinical trial demonstrated that intermittent cetuximab (IC) was a safe alternative to continuous cetuximab (CC), with less cytotoxic chemotherapy, in first-line treatment for KRAS wild-type metastatic colorectal cancer (mCRC). Cetuximab has been available for this indication in England since 2015, but treatment breaks beyond 6 weeks were prohibited, despite real-world evidence that therapy de-escalation maintains equivalent disease control, but with superior Quality-of-Life (QoL). We performed health economic analyses of IC versus CC and used this evidence to help underpin policy change and guide clinical practice through reduction in unnecessary treatment for mCRC patients. Read More

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Clinicopathological and molecular characteristics of RSPO fusion-positive colorectal cancer.

Br J Cancer 2022 Jun 17. Epub 2022 Jun 17.

Division of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.

Background: RSPO fusions that lead to WNT pathway activation are potential therapeutic targets in colorectal cancer (CRC), but their clinicopathological significance remains unclear.

Methods: We screened 1019 CRCs for RSPO fusions using multiplex reverse transcription-PCR. The RSPO fusion-positive tumours were subjected to whole-exome sequencing (WES). Read More

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Genomic landscape of pathogenic mutation of APC, KRAS, TP53, PIK3CA, and MLH1 in Indonesian colorectal cancer.

PLoS One 2022 16;17(6):e0267090. Epub 2022 Jun 16.

Department of General Surgery, Digestive Division, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.

Background: Colorectal cancer (CRC) needs several mutations to occur in various genes, and can vary widely in different individuals; hence it is essential to be discovered in a specific population. Until recently, there has been no known study describing APC, TP53, PIK3CA, KRAS, and MLH1 of CRC in Indonesian population. This study describes the nature and location of mutation in CRC patients treated at three different hospitals in Jakarta. Read More

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Application of histology-agnostic treatments in metastatic colorectal cancer.

Dig Liver Dis 2022 Jun 11. Epub 2022 Jun 11.

Department of Oncology and Hemato-Oncology, Milano, Università degli Studi di Milano Italy; Department of Hematology, Oncology, and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, 20162, Milan, Italy. Electronic address:

Cancer treatment is increasingly focused on targeting molecular alterations identified across different tumor histologies. While some oncogenic drivers such as microsatellite instability (MSI) and NTRK fusions are actionable with the very same approach regardless of tumor type ("histology-agnostic"), others require histology-specific therapeutic adjustment ("histology-tuned") by means of adopting specific inhibitors and ad hoc combinations. Among histology-agnostic therapies, pembrolizumab or dostarlimab demonstrated comparable activity in MSI metastatic colorectal cancer (mCRC) as in other tumors with MSI status (ORR 38% vs 40% and 36% vs 39%, respectively), while entrectinib or larotrectinib proved effective in NTRK rearranged mCRC even though less dramatically than in the overall population (ORR 20% vs 57%, and 50% vs 78%, respectively). Read More

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Characterizing the G12C mutation in metastatic colorectal cancer: a population-based cohort and assessment of expression differences in The Cancer Genome Atlas.

Ther Adv Med Oncol 2022 6;14:17588359221097940. Epub 2022 Jun 6.

BC Cancer, The University of British Columbia, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.

Introduction: In metastatic colorectal cancer (mCRC), mutations impart inferior survival and resistance to anti-epidermal growth factor receptor (EGFR) antibodies. G12C inhibitors have been developed and we evaluated how G12C differs from other RAS mutations.

Patients And Methods: This retrospective review evaluated patients in British Columbia, Canada with mCRC and testing performed between 1 January 2016 and 31 December 2018. Read More

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Early-Stage Loss of GALNT6 Predicts Poor Clinical Outcome in Colorectal Cancer.

Front Oncol 2022 27;12:802548. Epub 2022 May 27.

Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States.

Colorectal adenocarcinomas arise from luminal lining epithelium of the colorectal tract which is covered with highly glycosylated mucins. Mucin O-glycosylation is initiated by a family of polypeptide N-acteylgalactosaminyltransferases (GALNTs). This study examined GALNT6 protein expression in 679 colorectal tumors, including 574 early-stage and 105 late-stage cancers. Read More

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Novel Potent EGFR-JAK3 Dual-Target Inhibitor that Overcomes KRAS Mutation Resistance in Colorectal Cancer.

Anticancer Agents Med Chem 2022 Jun 9. Epub 2022 Jun 9.

Department of Haematology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China.

Background: In-depth and clear mechanistic study is a prerequisite for new drugs to enter clinical research.

Method: New chemical entity BY4008 was identified by our lab as novel and highly potent EGFR and JAK3 dual-target inhibitor. In a cell-based test, it exhibited strong antiproliferative activities against SW620 and HCT116 colon cancer cells harboring KRAS mutation with IC50 of nanomolar potency. Read More

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Effect of KRAS codon 12 or 13 mutations on survival with trifluridine/tipiracil in pretreated metastatic colorectal cancer: a meta-analysis.

ESMO Open 2022 Jun 7;7(3):100511. Epub 2022 Jun 7.

Department of Medical Oncology, Dana Farber Cancer Institute, Boston, USA.

Background: KRAS gene mutations can predict prognosis and treatment response in patients with metastatic colorectal cancer (mCRC).

Methods: We undertook a meta-analysis of three randomized, placebo-controlled trials (RECOURSE, TERRA and J003) to investigate the impact of KRAS mutations in codons 12 or 13 on overall survival (OS) and progression-free survival in patients receiving trifluridine/tipiracil (FTD/TPI) for refractory mCRC.

Results: A total of 1375 patients were included, of whom 478 had a KRAS codon 12 mutation and 130 had a KRAS codon 13 mutation. Read More

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Dynamic changes in RAS gene status in circulating tumour DNA: a phase II trial of first-line FOLFOXIRI plus bevacizumab for RAS-mutant metastatic colorectal cancer (JACCRO CC-11).

ESMO Open 2022 Jun 7;7(3):100512. Epub 2022 Jun 7.

Division of Medical Oncology, Showa University Fujigaoka Hospital, Yokohama, Japan.

Background: Few prospective studies have used liquid biopsy testing in RAS-mutant metastatic colorectal cancer (mCRC), and its clinical significance remains unknown. Therefore, this study aimed to carry out a biomarker analysis by liquid biopsy using updated data of the phase II trial of FOLFOXIRI plus bevacizumab as first-line chemotherapy for RAS-mutant mCRC.

Materials And Methods: A total of 64 patients who received modified FOLFOXIRI regimen (irinotecan 150 mg/m, oxaliplatin 85 mg/m, levofolinate 200 mg/m, and fluorouracil 2400 mg/m) plus bevacizumab biweekly were enrolled. Read More

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Effect of KRAS mutations and p53 expression on the postoperative prognosis of patients with colorectal cancer.

Mol Genet Genomic Med 2022 Jun 10:e1905. Epub 2022 Jun 10.

Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.

Background: In the occurrence and development of colorectal cancer, p53 is an important regulator downstream of the MAPK signaling pathway and plays an important role in inhibiting abnormal proliferation signals generated by KRAS mutations. The purpose of this study is to explore the correlation between KRAS mutations and p53 expression and evaluate their prognosis values in colorectal cancer.

Methods: PCR technology and immunohistochemical (IHC) staining were used to detect KRAS mutation status and p53 expression level in 266 specimens of colorectal adenocarcinoma. Read More

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Multivariate Risk Analysis of RAS, BRAF and EGFR Mutations Allelic Frequency and Coexistence as Colorectal Cancer Predictive Biomarkers.

Cancers (Basel) 2022 Jun 4;14(11). Epub 2022 Jun 4.

Department of General Surgery, University of Medicine and Pharmacy "Carol Davila" Bucharest, 8 Blvd., Eroii Sanitari, 050474 Bucharest, Romania.

Background: Biomarker profiles should represent a coherent description of the colorectal cancer (CRC) stage and its predicted evolution.

Methods: Using droplet digital PCR, we detected the allelic frequencies (AF) of KRAS, NRAS, BRAF, and EGFR mutations from 60 tumors. We employed a pair-wise association approach to estimate the risk involving AF mutations as outcome variables for clinical data and as predicting variables for tumor-staging. Read More

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Characterization of stem cell landscape and identification of stemness-relevant prognostic gene signature to aid immunotherapy in colorectal cancer.

Stem Cell Res Ther 2022 Jun 9;13(1):244. Epub 2022 Jun 9.

Department of General Surgery, Peking University First Hospital, Peking University, Beijing, People's Republic of China.

Background: It is generally accepted that colorectal cancer (CRC) originates from cancer stem cells (CSCs), which are responsible for CRC progression, metastasis and therapy resistance. The high heterogeneity of CSCs has precluded clinical application of CSC-targeting therapy. Here, we aimed to characterize the stemness landscapes and screen for certain patients more responsive to immunotherapy. Read More

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Tumor profiling of KRAS, BRAF, and NRAS gene mutations in patients with colorectal cancer: A Lebanese major center cohort study.

Gene 2022 Aug 6;834:146646. Epub 2022 Jun 6.

Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon. Electronic address:

Background: In the era of precision medicine, treatment schemes for advanced Colorectal (CRC) disease include monoclonal antibodies which block the epidermal growth factor receptor (EGFR) implicated in tumor proliferation, invasion, migration and neovascularization. Resistance to these agents has been correlated with activating downstream mutations in KRAS, BRAF and NRAS genes, among others, leading to constitutive activation of the EGFR axis bypassing EGFR blockade. The assessment of tumor RASandBRAFmutational status has thus become standard clinical practice. Read More

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MLH1, BRAF and p53 - searching for significant markers to predict evolution towards adenocarcinoma in colonic sessile serrated lesions.

Rom J Morphol Embryol 2021 Oct-Dec;62(4):971-979

Department of Pathology, Colentina University Hospital, Bucharest, Romania;

Background And Aim: Colonic serrated lesions are premalignant lesions, using an alternative malignization pathway, including multiple genetic and epigenetic alterations, as: mismatch repair deficiency due to MutL homolog 1 (MLH1) promoter methylation, tumor protein p53 (TP53) mutations, activating mutations of v-Raf murine sarcoma viral oncogene homolog B (BRAF) and Kirsten rat sarcoma viral oncogene homolog (KRAS). Our study aims to evaluate MLH1, BRAF and p53 immunohistochemical (IHC) status in sessile serrated lesions (SSLs), with and without dysplasia.

Materials And Methods: This is a retrospective case-control study including 20 SSLs with dysplasia and 20 SSLs without dysplasia (matching sex and age). Read More

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