4,892 results match your criteria Colorectal Cancer and KRAS


Current therapy of advanced colorectal cancer according to RAS/RAF mutational status.

Cancer Metastasis Rev 2020 Jul 9. Epub 2020 Jul 9.

Department of Oncology, South-Pest Hospital Centre - National Institute for Infectology and Haematology, Budapest, Hungary.

Colorectal cancer is a clinically and molecularly heterogeneous disease. Currently, extended RAS and BRAF mutation testing is obligatory in routine clinical practice before starting any treatment in the metastatic setting. Treatment decision making also includes assessment of the clinical condition of the patient, definition of the treatment goal, and consideration of the primary tumor site. Read More

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http://dx.doi.org/10.1007/s10555-020-09913-7DOI Listing

KRAS Mutation-Responsive miR-139-5p inhibits Colorectal Cancer Progression and is repressed by Wnt Signaling.

Theranostics 2020 5;10(16):7335-7350. Epub 2020 Jun 5.

State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.

Colorectal cancer (CRC) frequently harbors KRAS mutations that result in chemoresistance and metastasis. MicroRNAs (miRNAs) are usually dysregulated and play important regulatory roles in tumor progression. However, the KRAS mutation-responsive miRNA profile in CRC remains uninvestigated. Read More

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http://dx.doi.org/10.7150/thno.45971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330859PMC

Survival benefit of surgical resection after first-line triplet chemotherapy and bevacizumab in patients with initially unresectable metastatic colorectal cancer.

World J Surg Oncol 2020 Jul 8;18(1):163. Epub 2020 Jul 8.

Medical Oncology Section, Oncology Centre, King Faisal Specialist Hospital and Research Centre, PO Box 3354, Riyadh, 11211, Saudi Arabia.

Background: Surgical resection of metastatic disease in patients with initially non-resectable colorectal cancer (CRC) has improved overall survival. Intensified chemotherapy regimens have increased the probability of converting unresectable metastasis to resectable. Here, we report the result of combining intensive chemotherapy (triplet) and surgical resection of metastatic lesions in patients with metastatic CRC. Read More

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http://dx.doi.org/10.1186/s12957-020-01930-8DOI Listing

Characterization of Chilean patients with sporadic colorectal cancer according to the three main carcinogenic pathways: Microsatellite instability, CpG island methylator phenotype and Chromosomal instability.

Tumour Biol 2020 Jul;42(7):1010428320938492

Coloproctology Unit, Clínica Las Condes, Santiago, Chile.

Molecular classification of colorectal cancer is difficult to implement in clinical settings where hundreds of genes are involved, and resources are limited. This study aims to characterize the molecular subtypes of patients with sporadic colorectal cancer based on the three main carcinogenic pathways microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and chromosomal instability (CIN) in a Chilean population. Although several reports have characterized colorectal cancer, most do not represent Latin-American populations. Read More

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http://dx.doi.org/10.1177/1010428320938492DOI Listing

Multicenter Single-Arm, Two-Stage Phase 2 Study of Panitumumab in Patients With Cetuximab-Refractory Metastatic Colorectal Cancer: The PACER Trial.

Clin Colorectal Cancer 2020 May 29. Epub 2020 May 29.

U.O.C. Oncologia, Ospedale del Mare, Napoli, Italy. Electronic address:

Purpose: To assess whether panitumumab is active in patients with cetuximab-refractory metastatic colorectal cancer (mCRC).

Patients And Methods: Eligible patients had pretreated RAS (renin-angiotensin system) wild-type mCRC that progressed after cetuximab treatment, after having shown either objective response or stable disease. A minimax two-stage design was applied, with progression-free rate at 2 months as the primary end point. Read More

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http://dx.doi.org/10.1016/j.clcc.2020.05.009DOI Listing

Single Nucleotide Polymorphisms in MiRNA Binding Sites of Nucleotide Excision Repair-Related Genes Predict Clinical Benefit of Oxaliplatin in FOLFOXIRI Plus Bevacizumab: Analysis of the TRIBE Trial.

Cancers (Basel) 2020 Jun 30;12(7). Epub 2020 Jun 30.

Division of Medical Oncology Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.

Background: The nucleotide excision repair (NER) pathway participates in platinum-induced DNA damage repair. Single nucleotide polymorphisms (SNPs) in miRNA-binding sites in the NER genes and are associated with the risk of colorectal cancer (CRC). Here, we analyzed whether and SNPs predict the efficacy of oxaliplatin in metastatic CRC (mCRC) patients. Read More

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http://dx.doi.org/10.3390/cancers12071742DOI Listing

Oncogenic mutation in RAS-RAF axis leads to increased expression of GREB1 resulting in tumor proliferation in CRC.

Cancer Sci 2020 Jul 6. Epub 2020 Jul 6.

Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.

BRAF mutation accounts for up to 90 % of all BRAF mutations in human colorectal cancer (CRC), and constitutively activates the MEK-MAPK pathway. It is recognized that neutralizing monoclonal antibodies for epidermal growth factor receptor alone are not effective for CRC with BRAF mutation. Therefore, there are increasing interests in identification of the possible therapeutic targets in downstream of BRAF mutation in CRCs. Read More

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http://dx.doi.org/10.1111/cas.14558DOI Listing

Dual inhibition of VEGF and PARP suppresses KRAS-mutant colorectal cancer.

Neoplasia 2020 Jul 3;22(9):365-375. Epub 2020 Jul 3.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China. Electronic address:

The addition of bevacizumab to chemotherapy has prolonged overall and progression-free survival rates for metastatic colorectal cancer (mCRC). However, KRAS-mutant (KRAS-mut) CRC, lacking an ideal targeted agent, represents an inferior-response subgroup of patients. In the present study, we investigated a combination approach of bevacizumab + olaparib in KRAS-mut CRC in a preclinical setting. Read More

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http://dx.doi.org/10.1016/j.neo.2020.06.001DOI Listing

KRAS, NRAS, and BRAF mutation prevalence, clinicopathological association, and their application in a predictive model in Mexican patients with metastatic colorectal cancer: A retrospective cohort study.

PLoS One 2020 6;15(7):e0235490. Epub 2020 Jul 6.

Genetics Laboratory, Vitagénesis SA de CV, Monterrey, Nuevo Leon, Mexico.

Mutations in KRAS, NRAS, and BRAF (RAS/BRAF) genes are the main predictive biomarkers for the response to anti-EGFR monoclonal antibodies (MAbs) targeted therapy in metastatic colorectal cancer (mCRC). This retrospective study aimed to report the mutational status prevalence of these genes, explore their possible associations with clinicopathological features, and build and validate a predictive model. To achieve these objectives, 500 mCRC Mexican patients were screened for clinically relevant mutations in RAS/BRAF genes. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235490PLOS

Genomic alterations of NTRK, POLE, ERBB2 and MSI status in Chinese colorectal cancers.

Oncologist 2020 Jul 6. Epub 2020 Jul 6.

Shu Lan (Hangzhou) hospital, Hangzhou, Zhejiang Province, China.

Background The increasing molecular characterization of colorectal cancers (CRC) has spurred the need to look beyond RAS, BRAF, and microsatellite instability (MSI). Genomic alterations, including ERBB2 amplifications and mutations, POLE mutations, MSI, and NTRK1-3 fusions, have emerged as targets for matched therapies. We sought to study a clinically annotated Chinese cohort of CRC subjected to genomic profiling to explore relative target frequencies. Read More

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http://dx.doi.org/10.1634/theoncologist.2020-0356DOI Listing

Germline and Somatic Pharmacogenomics to Refine Rectal Cancer Patients Selection for Neo-Adjuvant Chemoradiotherapy.

Front Pharmacol 2020 17;11:897. Epub 2020 Jun 17.

Clinical and Experimental Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.

Neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery is the standard of care for patients with Locally Advanced Rectal Cancer (LARC). Current selection for nCRT is based on clinical criteria regardless of any molecular marker. Pharmacogenomics may be a useful strategy to personalize and optimize nCRT in LARC. Read More

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http://dx.doi.org/10.3389/fphar.2020.00897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311751PMC

NRAS mutant E132K identified in young-onset sporadic colorectal cancer and the canonical mutants G12D and Q61K affect distinct oncogenic phenotypes.

Sci Rep 2020 Jul 3;10(1):11028. Epub 2020 Jul 3.

Disease Molecular Biology and Epigenetics Laboratory, National Institute of Molecular Biology and Biotechnology, University of the Philippines Diliman, Ma. Regidor St., National Science Complex, 1101, Quezon City, Philippines.

Recent data show a global increase in colorectal cancer (CRC) cases among younger demographics, which portends poorer prognosis. The cause of rising incidence is uncertain, and its mutational landscape remains largely unexplored, including those in genes of the epidermal growth factor receptor pathway. Among these are NRAS mutants where there is paucity of functional studies compared to KRAS. Read More

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http://dx.doi.org/10.1038/s41598-020-67796-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334206PMC

Expression of transcript variants as a potential biomarker for colorectal cancer.

Biomark Med 2020 Jul 2. Epub 2020 Jul 2.

Centre of Marine Sciences, University of Algarve, Faro, Portugal.

To provide novel data on the expression of transcripts in colorectal cancer (CRC) tissues and to explore their potential as biomarkers. transcripts expression was determined by quantitative real-time PCR in tissues from 28 CRC patients. Their association with clinicopathological factors and survival analysis was performed. Read More

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http://dx.doi.org/10.2217/bmm-2019-0369DOI Listing

Reduced replication origin licensing selectively kills KRAS-mutant colorectal cancer cells via mitotic catastrophe.

Cell Death Dis 2020 Jul 1;11(7):499. Epub 2020 Jul 1.

Institute of Pathology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.

To unravel vulnerabilities of KRAS-mutant CRC cells, a shRNA-based screen specifically inhibiting MAPK pathway components and targets was performed in CaCo2 cells harboring conditional oncogenic KRAS. The custom-designed shRNA library comprised 121 selected genes, which were previously identified to be strongly regulated in response to MEK inhibition. The screen showed that CaCo2 cells expressing KRAS were sensitive to the suppression of the DNA replication licensing factor minichromosome maintenance complex component 7 (MCM7), whereas KRAS CaCo2 cells were largely resistant to MCM7 suppression. Read More

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http://dx.doi.org/10.1038/s41419-020-2704-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330027PMC
July 2020
5.014 Impact Factor

KRAS G12C Metastatic Colorectal Cancer: Specific Features of a New Emerging Target Population.

Clin Colorectal Cancer 2020 May 12. Epub 2020 May 12.

Department of Oncology, Veneto Institute of Oncology IOV IRCCS, Padua, Italy. Electronic address:

Background: Kirsten rat sarcoma viral oncogene (KRAS) G12C mutation occurs in about 4% of colorectal cancers (CRCs). Recently, KRAS G12C was identified to be a potential drug target and predictor of response to the novel on AMG510 target treatment. We described the clinicopathologic features and prognosis of KRAS G12C-mutated metastatic CRCs compared to other KRAS mutation. Read More

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http://dx.doi.org/10.1016/j.clcc.2020.04.009DOI Listing

Efficacy of Panitumumab and Cetuximab in Patients with Colorectal Cancer Previously Treated with Bevacizumab; a Combined Analysis of Individual Patient Data from ASPECCT and WJOG6510G.

Cancers (Basel) 2020 Jun 28;12(7). Epub 2020 Jun 28.

Department of Medical Oncology, Queen Elizabeth Hospital and University of Adelaide, 5011 Woodville, Australia.

Background: Phase-III ASPECCT and randomised phase-II WJOG6510G trials demonstrated the noninferiority of panitumumab, when compared with cetuximab, for overall survival in patients with chemotherapy-refractory wild-type exon 2 metastatic colorectal cancer.

Methods: The subgroup that received bevacizumab either prior to panitumumab or cetuximab monotherapy (ASPECCT) or in combination with irinotecan (WJOG6510G) was included. Multivariate Cox models were created, including the treatment arms as covariates together with patient, disease and treatment characteristics. Read More

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http://dx.doi.org/10.3390/cancers12071715DOI Listing

DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome.

Cancers (Basel) 2020 Jun 28;12(7). Epub 2020 Jun 28.

Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic.

There is ample evidence for the essential involvement of DNA repair and DNA damage response in the onset of solid malignancies, including ovarian cancer. Indeed, highpenetrance germline mutations in DNA repair genes are important players in familial cancers: , mutations or mismatch repair, and polymerase deficiency in colorectal, breast, and ovarian cancers. Recently, some molecular hallmarks (e. Read More

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http://dx.doi.org/10.3390/cancers12071713DOI Listing

Discovery of Novel PDEδ Degraders for the Treatment of KRAS Mutant Colorectal Cancer.

J Med Chem 2020 Jun 30. Epub 2020 Jun 30.

KRAS-PDEδ protein-protein interaction represents an appealing target for cancer therapy. However, fast release of high-affinity inhibitors from PDEδ hampered drug binding affinity and antiproliferative activity. To overcome the limitations, the first proteolysis-targeting chimeric (PROTAC) small molecules targeting PDEδ were designed. Read More

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http://dx.doi.org/10.1021/acs.jmedchem.0c00929DOI Listing

Landscape of RAS Variations in 17,993 Pan-cancer Patients Identified by Next-generation Sequencing.

Pathol Oncol Res 2020 Jun 30. Epub 2020 Jun 30.

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, NO.300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, China.

RAS family genes (HRAS, KRAS and NRAS) were frequently observed in several tumors. The expression of constitutively active RAS proteins mediated by RAS variations promote the development of tumors. KRAS is an important prognostic and drug resistance biomarker. Read More

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http://dx.doi.org/10.1007/s12253-020-00845-9DOI Listing

Outcome of patients with colorectal cancer undergoing lung metastases resection: a single-institution retrospective analysis.

Tumori 2020 Jun 29:300891620930793. Epub 2020 Jun 29.

Department of Clinical and Experimental Oncology, Medical Oncology Unit 1, Istituto Oncologico Veneto (IRCSS), Padua, Italy.

Introduction: This study was undertaken to review a single-institution cohort of patients with metastatic colorectal cancer undergoing lung resection after a multidisciplinary evaluation and to investigate the main prognostic factors for survival.

Methods: Medical records of 129 patients undergoing lung metastasectomy for colorectal cancer with curative intent from 2001 to 2017 were reviewed. Tissue samples from the primary tumor were analyzed with a multiplex genotyping system for the detection of mutations in and genes. Read More

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http://dx.doi.org/10.1177/0300891620930793DOI Listing

and Concomitant Mutations in a Patient with Metastatic Colon Adenocarcinoma: An Interesting Case Report.

Case Rep Oncol 2020 May-Aug;13(2):595-600. Epub 2020 Jun 4.

Unità di Oncologia Medica, Ospedale S.G. Moscati, Taranto, Italy.

A 68-year-old female patient with tenesmus and blood in the stool was admitted to the S.G. Moscati Hospital of Taranto. Read More

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http://dx.doi.org/10.1159/000507882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315173PMC

KRAS Status is Associated with Metabolic Parameters in Metastatic Colorectal Cancer According to Primary Tumour Location.

Pathol Oncol Res 2020 Jun 27. Epub 2020 Jun 27.

Department of Gastroenterology, University Hospital Coventry and Warwickshire, Clifford Bridge Road, Coventry, CV2 2DX, UK.

Colorectal cancer (CRC) is characterized by complex interplay between macroenvironmental factors and tumour microenvironment, leading to variable outcomes in CRC patients. To date, there is still a need to identify macroenvironment/microenvironment factors that could define subgroup of patients that would benefit from specific anti-cancer treatment in order to improve patient selection for individualized targeted-based therapy. Aim of this study was to evaluate associations between metabolic parameters and KRAS status in metastatic CRC (mCRC) according to a new tumour site classification. Read More

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http://dx.doi.org/10.1007/s12253-020-00850-yDOI Listing

The diagnostic accuracy of digital PCR, ARMS and NGS for detecting KRAS mutation in cell-free DNA of patients with colorectal cancer: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2020 Jun;99(26):e20708

Department of Physiology, College of Medicine, Chengdu University, Chengdu, China.

Introduction: Cetuximab and panitumumab have been used clinically to treat metastatic colorectal cancer for more than 15 years. Before the treatment is given, it is required to determine the KRAS mutation status since it would lead to drug resistance. Tumor tissue sample is traditionally used for cancer genotyping. Read More

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http://dx.doi.org/10.1097/MD.0000000000020708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328928PMC
June 2020
5.723 Impact Factor

Clinicopathological Characteristics and Mutation Spectrum of Colorectal Adenocarcinoma With Mucinous Component in a Chinese Cohort: Comparison With Classical Adenocarcinoma.

Front Oncol 2020 9;10:917. Epub 2020 Jun 9.

Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Colorectal adenocarcinoma with mucinous component (AWMC) is a special entity of colorectal cancer. The study is aimed at analyzing the clinicopathological characteristics, mutation spectrum, and prognosis of AWMC and comparing it with classical adenocarcinoma (AC) in a Chinese cohort. One hundred eight AMWC and 204 AC patients were included. Read More

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http://dx.doi.org/10.3389/fonc.2020.00917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296099PMC

Effect of PIERCE1 on colorectal cancer.

Exp Anim 2020 Jun 25. Epub 2020 Jun 25.

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University.

Colorectal cancer is the second most lethal cancer type across all ages and sexes, the many mechanisms of which are still currently being further elucidated. PIERCE1 has been known to be involved in the cell cycle and proliferation, the expression of which is regulated by stress conditions in a p53-dependent manner. Through a database search, we found that PIERCE1 was significantly augmented in patients with colorectal carcinoma compared to normal samples, suggesting its possible role in tumor regulation. Read More

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http://dx.doi.org/10.1538/expanim.19-0155DOI Listing

Analysis of cancer-related mutations in extracellular vesicles RNA by Droplet Digital™ PCR.

Biotechniques 2020 Jun 25. Epub 2020 Jun 25.

Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin & Berlin Institute of Health, Charité Comprehensive Cancer Center, Berlin, Germany.

Extracellular vesicles (EVs) are taking their place as potential biomarkers in the field of liquid biopsy. In this study, EVs were isolated from plasma samples of 31 patients with colorectal cancer and melanoma via differential centrifugation and Droplet Digital™ PCR (Bio-Rad, CA, USA) was used to profile V600E/K, G12A/C/D/V and  G13D mutations from EV-derived cDNA. The concordance rates with corresponding tissue were 54% and 44% in the colorectal cancer and melanoma cohort, respectively. Read More

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http://dx.doi.org/10.2144/btn-2020-0028DOI Listing

Evolving pathologic concepts of serrated lesions of the colorectum.

J Pathol Transl Med 2020 Jun 26. Epub 2020 Jun 26.

Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Here, we provide an up-to-date review of the histopathology and molecular pathology of serrated colorectal lesions. First, we introduce the updated contents of the 2019 World Health Organization classification for serrated lesions. The sessile serrated lesion (SSL) is a new diagnostic terminology that replaces sessile serrated adenoma and sessile serrated polyp. Read More

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http://dx.doi.org/10.4132/jptm.2020.04.15DOI Listing

Active Compound of Semen ( Seeds) Suppressed KRAS-Driven Colorectal Cancer and Restored Muscle Cell Function during Cancer Progression.

Molecules 2020 Jun 22;25(12). Epub 2020 Jun 22.

Department of Food Biotechnology, School of Medical and Life Science, Silla University, Busan 46958, Korea.

Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven colorectal cancer (CRC) is notorious to target with drugs and has shown ineffective treatment response. The seeds of also known as morning glory, have been used as traditional medicine in East Asia. We focused on whether seeds have a suppressive effect on mutated KRAS-driven CRC as well as reserving muscle cell functions during CRC progression. Read More

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http://dx.doi.org/10.3390/molecules25122864DOI Listing

Drastic Reduction of Turnaround Time After Implementation of a Fully Automated Assay for RAS-BRAF Mutations in Colorectal Cancer: A Pilot Prospective Study in Real-life Conditions.

Pathol Oncol Res 2020 Jun 22. Epub 2020 Jun 22.

Rouen University Hospital, Rouen, France.

In some situations, there is a need for rapid mutation tests for guiding clinical decisions and starting targeted therapies with minimal delays. In this study we evaluated the turnaround time before and after the implementation of a fully automated multiplex assay for KRAS and NRAS/BRAF mutation tests (Idylla™ platform, Biocartis) in metastatic colorectal cancer. The objective of this project was to compare the turnaround times in 2017-2018 with the fully automated multiplex assay to the 2016 results with previous methods. Read More

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http://dx.doi.org/10.1007/s12253-020-00818-yDOI Listing

Tensin4 (TNS4) is upregulated by Wnt signalling in adenomas in multiple intestinal neoplasia (Min) mice.

Int J Exp Pathol 2020 Jun 22. Epub 2020 Jun 22.

Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.

Apc mice are regarded as a standard animal model of colorectal cancer (CRC). Tensin4 (TNS4 or Cten) is a putative oncogene conferring features of stemness and promoting motility. Our objective was to assess TNS4 expression in intestinal adenomas and determine whether TNS4 is upregulated by Wnt signalling. Read More

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http://dx.doi.org/10.1111/iep.12352DOI Listing

Clinicopathological and mutational differences between tumors with multiple metastases and single lung metastasis in colorectal cancer.

Oncol Lett 2020 Jul 14;20(1):541-550. Epub 2020 May 14.

Department of Human Pathology, Juntendo University, Graduate School of Medicine, Tokyo 113-8421, Japan.

Cancer metastasis, particularly multiple metastatic cancer, is a significant event that affects patient prognosis. However, single metastasis can be treated by partial resection, although the clinicopathological and molecular profile of single lung metastasis has not been thoroughly elucidated. The present study examined tumor heterogeneity by comparing the mutation status between primary colorectal cancer (CRC) and corresponding metastatic lesions to identify prognostic factors associated with single lung metastasis and multiple metastases. Read More

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http://dx.doi.org/10.3892/ol.2020.11627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285844PMC

Quadruplicate Synchronous Adenocarcinoma of the Colon with Distant Metastases-Long-Term Molecular Follow-Up by KRAS and TP53 Mutational Profiling.

Diagnostics (Basel) 2020 Jun 16;10(6). Epub 2020 Jun 16.

Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.

Anatomically independent tumor foci represent biologically distinct neoplasias, potentially featured by different progressivity and treatment responsiveness. To demonstrate the biological complexity, a metastatic colon adenocarcinoma patient originally presenting with four independent primary tumors of the right colon half and altogether eight distant metastases was followed by molecular testing. Next-generation sequencing results highlighted the mutational profile of the individual primaries and the dynamics of the different gene variants observed during follow-up. Read More

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http://dx.doi.org/10.3390/diagnostics10060407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345140PMC

DKK2 blockage-mediated immunotherapy enhances anti-angiogenic therapy of Kras mutated colorectal cancer.

Biomed Pharmacother 2020 Jul 20;127:110229. Epub 2020 May 20.

Department of Pharmacology and Vascular Biology and Therapeutic Program, Yale School of Medicine, New Haven, CT, United States. Electronic address:

There are limited options for targeted therapies for colorectal cancer (CRC). Anti-EGFR therapy is limited to CRC without KRAS mutations. Even worse, most of CRC are refractory to currently immune checkpoint blockade. Read More

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http://dx.doi.org/10.1016/j.biopha.2020.110229DOI Listing

Combination of variations in inflammation- and endoplasmic reticulum-associated genes as putative biomarker for bevacizumab response in KRAS wild-type colorectal cancer.

Sci Rep 2020 Jun 17;10(1):9778. Epub 2020 Jun 17.

Centre for Systems Medicine and Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.

Chemotherapy combined with the angiogenesis inhibitor bevacizumab (BVZ) is approved as a first-line treatment in metastatic colorectal cancer (mCRC). Limited clinical benefit underpins the need for improved understanding of resistance mechanisms and the elucidation of novel predictive biomarkers. We assessed germline single-nucleotide polymorphisms (SNPs) in 180 mCRC patients (Angiopredict [APD] cohort) treated with combined BVZ + chemotherapy and investigated previously reported predictive SNPs. Read More

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http://dx.doi.org/10.1038/s41598-020-65869-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299973PMC

Immune characterization of metastatic colorectal cancer patients post reovirus administration.

BMC Cancer 2020 Jun 18;20(1):569. Epub 2020 Jun 18.

Montefiore Medical Center, 1695 Eastchester Road, Bronx, NY, 10461, USA.

Background: KRAS mutations are prevalent in 40-45% of patients with colorectal cancer (CRC) and targeting this gene has remained elusive. Viruses are well known immune sensitizing agents. The therapeutic efficacy of oncolytic reovirus in combination with chemotherapy is examined in a phase 1 study of metastatic CRC. Read More

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http://dx.doi.org/10.1186/s12885-020-07038-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301987PMC

Genomic profiling of microRNA target genes in colorectal cancer.

Tumour Biol 2020 Jun;42(6):1010428320933512

Plant Omics Group, Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Bellville, South Africa.

Colorectal cancer is the second and third most common cancer in men and women, respectively, worldwide. Alterations such as genetic and epigenetic are common in colorectal cancer and are the basis of tumor formation. The exploration of the molecular basis of colorectal cancer can drive a better understanding of the disease as well as guide the prognosis, therapeutics, and disease management. Read More

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http://dx.doi.org/10.1177/1010428320933512DOI Listing

Is There Any Correlation Among MKK4 Expression, Clinicopathological Features & KRAS / NRAS mutation in Colorectal Cancer.

Expert Rev Mol Diagn 2020 Jun 19. Epub 2020 Jun 19.

Ankara Numune Training and Research Hospital , Department of Medical Oncology, Ankara, Turkey.

Background: We aimed to evaluate the correlation between MKK4 expression & clinicopathological features, KRAS/NRAS mutation in colorectal cancer.

Methods: MKK4 expression was assessed by immunoreactivity score(IRS). Staining intensity(SI) & percentage of positively stained cells(PP) were used for IRS (IRS = SIxPP). Read More

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http://dx.doi.org/10.1080/14737159.2020.1784728DOI Listing

Incorporating traditional and emerging biomarkers in the clinical management of metastatic colorectal cancer: an update.

Expert Rev Mol Diagn 2020 Jun 22:1-11. Epub 2020 Jun 22.

Department of Medical Oncology, Vall d'Hebron University Hospital , Barcelona, Spain.

Introduction: Molecular profiling has led to significantly longer survival in metastatic colorectal cancer (mCRC) patients. Clinical guidelines recommend testing for KRAS/NRAS, BRAF and MSI status, and new biomarkers such as HER2 amplification and NTRK fusions have emerged more recently in refractory CRC, supported by overwhelming clinical relevance. These biomarkers can guide treatment management to improve clinical outcomes in these patients. Read More

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http://dx.doi.org/10.1080/14737159.2020.1782194DOI Listing

Identification of as the Hub Gene Associated with KRAS Mutation in Colorectal Cancer by Coexpression Analysis.

DNA Cell Biol 2020 Jun 16. Epub 2020 Jun 16.

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Colorectal cancer (CRC) patients with KRAS mutation are refractory and usually have poor prognosis. We aimed to identify the hub gene associated with KRAS mutant CRCs. Weighted gene coexpression network analysis (WGCNA) was used to calculate the key module and the hub genes in GSE39582. Read More

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http://dx.doi.org/10.1089/dna.2020.5574DOI Listing

Chemotherapeutic Effectiveness of Combining Cetuximab for Metastatic Colorectal Cancer Treatment: A System Review and Meta-Analysis.

Front Oncol 2020 28;10:868. Epub 2020 May 28.

Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, China.

This meta-analysis used the database including PubMed, Medline, Cochrane Library, CNKI, Chinese-Cqvip, and Wanfang for randomized controlled trials (RCTs) to investigate the clinical effectiveness for combining cetuximab treatment with chemotherapy for treating metastatic colorectal cancer (mCRC). A total of 12 RCTs involved 7,108 patients with mCRC were included. The patients received chemotherapy with (3,521 cases) or without cetuximab (3,587 cases). Read More

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http://dx.doi.org/10.3389/fonc.2020.00868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270202PMC

Prognostic value of KRAS mutation status in colorectal cancer patients: a population-based competing risk analysis.

PeerJ 2020 1;8:e9149. Epub 2020 Jun 1.

Department of Medical Oncology, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Zhejiang University, Hangzhou, Zhejiang, China.

Background: To use competing analyses to estimate the prognostic value of KRAS mutation status in colorectal cancer (CRC) patients and to build nomogram for CRC patients who had KRAS testing.

Method: The cohort was selected from the Surveillance, Epidemiology, and End Results database. Cumulative incidence function model and multivariate Fine-Gray regression for proportional hazards modeling of the subdistribution hazard (SH) model were used to estimate the prognosis. Read More

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http://dx.doi.org/10.7717/peerj.9149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271887PMC

Lineage reversion drives WNT independence in intestinal cancer.

Cancer Discov 2020 Jun 16. Epub 2020 Jun 16.

Medicine, Weill Cornell Medicine

The WNT pathway is a fundamental regulator of intestinal homeostasis and hyperactivation of WNT signaling is the major oncogenic driver in colorectal cancer (CRC). To date, there are no described mechanisms that bypass WNT dependence in intestinal tumors. Here, we show that while WNT suppression blocks tumor growth in most organoid and in vivo CRC models, the accumulation of CRC-associated genetic alterations enables drug resistance and WNT-independent growth. Read More

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http://dx.doi.org/10.1158/2159-8290.CD-19-1536DOI Listing

BRAF Mutated Colorectal Cancer: New Treatment Approaches.

Cancers (Basel) 2020 Jun 14;12(6). Epub 2020 Jun 14.

Medical Oncology Department, University Hospital Ramon y Cajal, 28034 Madrid, Spain.

Colon cancer is one of the most frequently diagnosed malignancies in adults, considering both its incidence and prevalence. Anatomically, the right colon is considered as being from the cecum to the splenic flexure, and the left colon is from the splenic flexure to the rectum. Sidedness is a surrogate of a wide spectrum of colorectal cancer (CRC) biology features (embryology, microbiome, methylation, microsatellite instability (MSI), BRAF, aging, KRAS, consensus molecular subtypes (CMS), etc. Read More

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http://dx.doi.org/10.3390/cancers12061571DOI Listing

Genetic alteration of colorectal adenoma-carcinoma sequence among gastric adenocarcinoma and dysplastic lesions in a patient with attenuated familial adenomatous polyposis.

Mol Genet Genomic Med 2020 Jun 16:e1348. Epub 2020 Jun 16.

Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.

Background: Familial adenomatous polyposis (FAP) is characterized by colorectal polyposis and adenocarcinoma that is frequently accompanied by extracolonic neoplasm. The risk of gastric carcinoma is increasing in Western FAP patients as well as Asian patients.

Methods: We report the case of an FAP patient with fundic gland polyposis who developed gastric adenocarcinoma and metachronous pyloric gland adenomas. Read More

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http://dx.doi.org/10.1002/mgg3.1348DOI Listing

[A New Era of Colorectal Cancer Treatment Being Led by a Precise Analysis of Somatic Mutational Profiles Including RAS, BRAF Mutation and Microsatellite Instability Status].

Authors:
Takeshi Nagasaka

Gan To Kagaku Ryoho 2020 Jun;47(6):861-869

Dept. of Clinical Oncology, Kawasaki Medical School.

In Japan, clinically, a decade has passed since KRAS exon 2 hotspot mutations could be measured as a companion diagnostic agent of an anti-epidermal growth factor receptor antibody to treat unresectable advanced colorectal cancer. Till now, not only KRAS exon 2, but also KRAS exon 3, 4 and NRAS exon 2-4 mutation, and BRAF mutation(V600E)are approved as insurance as a companion diagnostics tool. In addition to those somatic mutations observed in Ras-Raf signal cascade, the measurement of microsatellite instability status is also approved as a companion diagnostic to anti-programmed death-1 receptor antibodies. Read More

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AMG 510 Shows Activity beyond NSCLC.

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Cancer Discov 2020 Jun 15. Epub 2020 Jun 15.

The latest results from the CodeBreak 100 trial evaluating AMG 510 indicate that this first-in-class KRAS inhibitor, having shown promise in non-small cell lung cancer, is modestly active in several other types of solid tumors, including colorectal cancer. Read More

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http://dx.doi.org/10.1158/2159-8290.CD-NB2020-061DOI Listing

The Coexistence of RAS and BRAF Mutations in Metastatic Colorectal Cancer: A Case Report and Systematic Literature Review.

J Gastrointestin Liver Dis 2020 Jun 3;29(2):251-256. Epub 2020 Jun 3.

Titu Maiorescu University of Medicine, Bucharest; Oncology Dept., Fundeni Clinical Institute, Bucharest, Romania.

Background And Aims: The coexistence of RAS and BRAF mutations is extremely rare, occurring in approximately 0.05% of patients with metastatic colorectal cancer (mCRC). Starting from a case presentation, this review aims to examine the prevalence, clinical, histopathological and molecular features of tumors with concomitant mutations. Read More

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http://dx.doi.org/10.15403/jgld-1003DOI Listing

Allele Facilitates the Metastasis of KRAS-Mutant Colorectal Cancer.

Front Genet 2020 26;11:511. Epub 2020 May 26.

McGovern Medical School, The University of Texas, Houston, TX, United States.

Major histocompatibility complex (HLA) class I chain-related protein A (MICA) regulates immune surveillance through activation of NKG2D (natural killer group 2D) receptor. However, the genetic association, potential function, and predictive ability of MICA alleles with colorectal cancer (CRC) prognosis remain undefined. In this study, we characterized MICA alleles in tissue samples from 104 patients with CRC and 536 healthy controls and carried out genetic association studies by molecular and clinical CRC phenotypes. Read More

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http://dx.doi.org/10.3389/fgene.2020.00511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264413PMC

Randomised phase II study of panitumumab plus irinotecan versus cetuximab plus irinotecan in patients with KRAS wild-type metastatic colorectal cancer refractory to fluoropyrimidine, irinotecan and oxaliplatin (WJOG 6510G).

Eur J Cancer 2020 Jun 8;135:11-21. Epub 2020 Jun 8.

Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: Cetuximab has been shown to be clinically active when given in combination with irinotecan in patients with irinotecan-refractory metastatic colorectal cancer (mCRC). However, it has remained unclear whether panitumumab is effective when combined with irinotecan. We compared efficacies of both regimens in this randomised phase II study. Read More

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http://dx.doi.org/10.1016/j.ejca.2020.04.014DOI Listing