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EGFR and colorectal cancer

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https://www.readbyqxmd.com/read/28936923/egfr-pathway-subgroups-in-chilean-colorectal-cancer-patients-detected-by-mutational-and-expression-profiles-associated-to-different-clinicopathological-features
#1
Karin Alvarez, Paulina Orellana, Cynthia Villarroel, Luis Contreras, Hiroshi Kawachi, Maki Kobayashi, Ana Maria Wielandt, Marjorie De la Fuente, Juan Carlos Triviño, Udo Kronberg, Pilar Carvallo, Francisco López-Köstner
Colorectal cancer is a multistep process affecting several signaling pathways including EGFR (epidermal growth factor receptor), a therapeutic target for metastatic disease. Our aim was to characterize the mutational and expression profiles of the EGFR pathway in colorectal tumors and to integrate these results according to five previously defined groups. We screened seven genes for mutations ( KRAS-BRAF-PIK3CA-PIK3R1-AKT1-MAP2K1-PTEN) and six proteins (EGFR-p110α-p85α-PTEN-phosphoAKT-phosphoMEK1) by immunohistochemistry, PTEN deletion, and MSI...
September 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28932126/dermopathy-associated-with-cetuximab-and-panitumumab-investigation-of-the-usefulness-of-moisturizers-in-its-management
#2
Shoichi Watanabe, Motoki Nakamura, Hiroki Takahashi, Masayasu Hara, Kei Ijichi, Daisuke Kawakita, Akimichi Morita
AIMS: Limited data regarding the objective evaluation of skin exsiccation caused by epidermal growth factor receptor (EGFR) inhibitors exist. Objective indices were applied to evaluate the usefulness of a moisturizer against skin exsiccation associated with the use of EGFR inhibitors in cancer patients. PATIENTS AND METHODS: Patients with either colorectal or head and neck cancer treated with either cetuximab or panitumumab were randomly assigned 1:2 to the prophylactic-treatment arm, where participants received prophylactical moisturizer treatment (heparinoid preparation, Hirudoid(®)), or to the symptomatic-treatment arm, where moisturizer was applied after the onset of cutaneous symptoms...
2017: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/28928860/the-impact-of-cetuximab-plus-akt-or-mtor-inhibitor-in-a-patient-derived-colon-cancer-cell-model-with-wild-type-ras-and-pik3ca-mutation
#3
Ju Sun Kim, Jung Eun Kim, Kyung Kim, Jeeyun Lee, Joon Oh Park, Ho Yeong Lim, Young Suk Park, Won Ki Kang, Seung Tae Kim
Background: Anti-EGFR therapies have been recommended for advanced colorectal cancer (CRC) with wild-type RAS and PIK3CA mutation. However, PIK3CA mutations are a poor prognostic marker and a negative predictor of response to anti-EGFR therapies in RAS wild-type CRC. Therefore, new and advanced treatment strategies are needed for personalized medical treatment of patients with wild-type RAS and PIK3CA mutation. Methods: Patient-derived tumor cells were collected from the ascites of a refractory colon cancer patient with wild-type RAS and PIK3CA mutation...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28916945/simvastatin-enhances-radiation-sensitivity-of-colorectal-cancer-cells
#4
Georgios Karagkounis, Jennifer DeVecchio, Sylvain Ferrandon, Matthew F Kalady
INTRODUCTION: Neoadjuvant chemoradiation (CRT) for rectal cancer induces variable responses, and better response has been associated with improved oncologic outcomes. Our group has previously shown that the administration of HMG-CoA reductase inhibitors, commonly known as statins, is associated with improved response to neoadjuvant CRT in rectal cancer patients. The purpose of this study was to study the effects of simvastatin on colorectal cancer cells and explore its potential as a radiation-sensitizer in vitro...
September 15, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28911069/clinical-utility-of-circulating-dna-analysis-for-rapid-detection-of-actionable-mutations-to-select-metastatic-colorectal-patients-for-anti-egfr-treatment
#5
A R Thierry, S El Messaoudi, C Mollevi, J L Raoul, R Guimbaud, D Pezet, P Artru, E Assenat, C Borg, M Mathonnet, C De La Fouchardière, O Bouché, C Gavoille, C Fiess, B Auzemery, R Meddeb, E Lopez-Crapez, C Sanchez, B Pastor, M Ychou
Background: While tumor-tissue remains the 'gold standard' for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care. Patients and methods: Concordance and data turnaround-time of ctDNA when compared with tumor-tissue analysis were studied in a real-time blinded prospective multicenter clinical study (n = 140 metastatic colorectal patients)...
September 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28903907/research-progress-on-genetic-heterogeneity-between-primary-and-paired-metastatic-colorectal-cancer
#6
You-Wang Lu, Kun-Hua Wang
Colorectal cancer (CRC) is one of the leading causes of cancer deaths in China. A standard practice in treating metastatic CRC (mCRC) is to predict benefits of the anti-EGFR monoclonal antibody treatment based on the somatic mutation spectrum. Because metastatic samples are difficult to obtain clinically, primary tumors are normally used instead. However, due to the genetic heterogeneity between primary and paired metastatic tumors, primary site biopsy always underrepresents the mutational landscape of metastatic sites...
June 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28884417/neratinib-first-global-approval
#7
Emma D Deeks
Neratinib (Nerlynx™) is an oral, irreversible inhibitor of the human epidermal growth factor receptors HER1 (EGFR), HER2 and HER4. The drug originally arose from research by Wyeth (now Pfizer) and is now being developed by Puma Biotechnology primarily for the treatment of HER2-positive (HER+) breast cancer. Neratinib is approved in the USA for the extended adjuvant treatment of patients with HER2+ early-stage breast cancer who have been previously treated with a trastuzumab-based adjuvant regimen, and is in the preregistration phase for this indication in the EU...
September 7, 2017: Drugs
https://www.readbyqxmd.com/read/28884286/combination-of-irinotecan-oxaliplatin-and-5-fluorouracil-as-a-rechallenge-regimen-for-heavily-pretreated-metastatic-colorectal-cancer-patients
#8
Gustavo Dos Santos Fernandes, Maria Ignez Braghiroli, Michelle Artioli, Ana Carolina Carvalho Rocha Paterlini, Marcela Crosara Teixeira, Brenda Pires Gumz, Daniel da Motta Girardi, Oddone F M Braghiroli, Frederico Perego Costa, Paulo M Hoff
PURPOSE: Our objective was to evaluate the benefit of re-exposing patients with refractory metastatic colorectal cancer (mCRC) to a combination of oxaliplatin, irinotecan and 5-fluorouracil treatment. METHODS: We retrospectively analysed patients with mCRC who received a combination of oxaliplatin, irinotecan and fluorouracil as a rechallenge regimen after progressing on the same drugs. Both FOLFOXIRI and FOLFIRINOX were used. Toxicity was evaluated for each treatment cycle, and survival analysis was performed using the Kaplan-Meier method...
September 8, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28869531/potential-application-of-eicosapentaenoic-acid-monoacylglyceride-in-the-management-of-colorectal-cancer
#9
Caroline Morin, Enrique Rodríguez, Pierre U Blier, Samuel Fortin
BACKGROUND: There is increasing evidence that marine omega-3 oils are involved in the reduction of cancer risk and progression. However, the anticancer effect of omega-3 monoglyceride on colorectal cancer has yet to be assessed. The goal of this study was to evaluate the anti-cancer effects of eicosapentaenoic acid monoglyceride (MAG-EPA) in HCT116 colorectal carcinoma cells. METHODS: The effect of MAG-EPA was evaluated in vitro on HCT116 cells and in vivo on mouse model of HCT116 xenograft...
September 4, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28858102/prognostic-value-of-kras-codon-13-gene-mutation-for-overall-survival-in-colorectal-cancer-direct-and-indirect-comparison-meta-analysis
#10
Min Seob Kwak, Jae Myung Cha, Jin Young Yoon, Jung Won Jeon, Hyun Phil Shin, Hye Jung Chang, Hyung Kyung Kim, Kwang Ro Joo, Joung Il Lee
BACKGROUND: The clinical significance of KRAS codon 13 mutation in patients with colorectal cancer (CRC) remains controversial. A systematic review and meta-analysis is necessary for a more precise estimation of the predictive role of KRAS codon 13 mutations in CRC patients. METHODS: We performed a systematic search using the MEDLINE, EMBASE, and Cochrane library databases from January 2000 to November 2016. The prognostic value of KRAS codon 13 mutation for overall survival (OS) was investigated by measuring the hazard ratio (HR) and 95% confidence interval (CI)...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28853050/clinical-pharmacokinetics-and-pharmacodynamics-of-the-epidermal-growth-factor-receptor-inhibitor-panitumumab-in-the-treatment-of-colorectal-cancer
#11
REVIEW
Sander Ketzer, Kirsten Schimmel, Miriam Koopman, Henk-Jan Guchelaar
Despite progress in the treatment of metastatic colorectal cancer (mCRC) in the last 15 years, it is still a condition with a relatively low 5-year survival rate. Panitumumab, a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFR), is able to prolong survival in patients with mCRC. Panitumumab is used in different lines of therapy in combination with chemotherapy, and as monotherapy for the treatment of wild-type (WT) RAS mCRC. It is administered as an intravenous infusion of 6 mg/kg every 2 weeks and has a t ½ of approximately 7...
August 29, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28852020/co-delivery-of-paclitaxel-and-cetuximab-by-nanodiamond-enhances-mitotic-catastrophe-and-tumor-inhibition
#12
Yu-Wei Lin, Emmanuel Naveen Raj, Wei-Siang Liao, Johnson Lin, Kuang-Kai Liu, Ting-Hua Chen, Hsiao-Chun Cheng, Chi-Ching Wang, Lily Yi Li, Chinpiao Chen, Jui-I Chao
The poor intracellular uptake and non-specific binding of anticancer drugs into cancer cells are the bottlenecks in cancer therapy. Nanocarrier platforms provide the opportunities to improve the drug efficacy. Here we show a carbon-based nanomaterial nanodiamond (ND) that carried paclitaxel (PTX), a microtubule inhibitor, and cetuximab (Cet), a specific monoclonal antibody against epidermal growth factor receptor (EGFR), inducing mitotic catastrophe and tumor inhibition in human colorectal cancer (CRC). ND-PTX blocked the mitotic progression, chromosomal separation, and induced apoptosis in the CRC cells; however, NDs did not induce these effects...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819429/map2k1-mutation-in-colorectal-cancer-patients-therapeutic-challenge-using-patient-derived-tumor-cell-lines
#13
J E Kim, K K Kim, S Y Kim, J Lee, S H Park, J O Park, Y S Park, H Y Lim, W K Kang, S T Kim
BACKGROUND: The MAP2K1 K57T mutation is known to be a potential mechanism of primary and secondary resistance to EGFR inhibitors in metastatic colorectal cancer (CRC) and has also been reported to promote resistance to BRAF and MEK inhibitors. It is important to overcome therapeutic resistance to EGFR inhibitors to improve the treatment outcomes of metastatic CRC. METHODS: We established patient-derived tumor cells (PDCs) from metastatic lesions that newly appeared during treatment with a BRAF inhibitor (LGX-818) plus an EGFR inhibitor (cetuximab) in a patient with BRAF-mutant CRC...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28807224/mesua-ferrea-stem-bark-extract-induces-apoptosis-and-inhibits-metastasis-in-human-colorectal-carcinoma-hct-116-cells-through-modulation-of-multiple-cell-signalling-pathways
#14
Muhammad Asif, Armaghan Shafaei, Aman Shah Abdul Majid, Mohammed Oday Ezzat, Saad S Dahham, Mohamed B Khadeer Ahamed, Chern Ein Oon, Amin Malik Shah Abdul Majid
Considering the great potential of natural products as anticancer agents, the present study was designed to explore the molecular mechanisms responsible for anticancer activities of Mesua ferrea stem bark extract against human colorectal carcinoma. Based on MTT assay results, bioactive sub-fraction (SF-3) was selected for further studies using HCT 116 cells. Repeated column chromatography resulted in isolation of less active α-amyrin from SF-3, which was identified and characterized by GC-MS and HPLC methods...
July 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28804596/characterisation-of-tumour-derived-microvesicles-in-cancer-patients-blood-and-correlation-with-clinical-outcome
#15
Kerstin Menck, Annalen Bleckmann, Astrid Wachter, Bianca Hennies, Lena Ries, Matthias Schulz, Marko Balkenhol, Tobias Pukrop, Bawarjan Schatlo, Ulrike Rost, Dirk Wenzel, Florian Klemm, Claudia Binder
To evaluate whether tumour-derived microvesicles (T-MV), originating from the plasma membrane, represent suitable cancer biomarkers, we isolated MV from peripheral blood samples of cancer patients with locally advanced and/or metastatic solid tumours (n = 330, including 79 head & neck cancers, 74 lung cancers, 41 breast cancers, 28 colorectal cancers and 108 with other cancer forms) and controls (n = 103). Whole MV preparations were characterised using flow cytometry. While MV carrying the tumour-associated proteins MUC1, EGFR and EpCAM were found to be enhanced in a tumour-subtype-specific way in patients' blood, expression of the matrix metalloproteinase inducer EMMPRIN was increased independent of tumour type...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28797274/the-pattern-of-kras-mutations-in-metastatic-colorectal-cancer-a-retrospective-audit-from-sri-lanka
#16
Nirmala Dushyanthi Sirisena, Kemal Deen, Dayupathi Eranda Nipunika Mandawala, Pumindu Herath, Vajira Harshadeva Weerabaddana Dissanayake
OBJECTIVE: Activating mutations in the KRAS gene, found in approximately 53% of metastatic colorectal cancer (mCRC) cases, can render epidermal growth factor receptor (EGFR) inhibitors ineffective. Regional differences in these mutations have been reported. This is the first study which aims to describe the pattern of KRAS mutations in a Sri Lankan cohort of mCRC patients. RESULTS: The KRAS genotypes detected in mCRC patients which have been maintained in an anonymized database were retrospectively analyzed...
August 10, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28794806/recent-developments-in-the-treatment-of-metastatic-colorectal-cancer
#17
REVIEW
Jonathan M Loree, Scott Kopetz
Over the past decade there have been significant advances in the molecular characterization of colorectal cancer (CRC) that are driving treatment decisions. Expanded RAS testing beyond KRAS exon 2 was established as crucial for identifying patients who will respond to anti-epidermal growth factor receptor (EGFR) therapies and low-frequency mutations in RAS/tumor heterogeneity are gaining recognition as potential mechanisms of resistance. Despite this progress, the fact that we do not understand why left-sided but not right-sided tumors have improved outcomes following anti-EGFR therapy highlights our superficial understanding of this disease...
August 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28794688/aberrantly-methylated-differentially-expressed-genes-and-pathways-in-colorectal-cancer
#18
Jingwei Liu, Hao Li, Liping Sun, Zhenning Wang, Chengzhong Xing, Yuan Yuan
BACKGROUND: Methylation plays an important role in the etiology and pathogenesis of colorectal cancer (CRC). This study aimed to identify aberrantly methylated-differentially expressed genes (DEGs) and pathways in CRC by comprehensive bioinformatics analysis. METHODS: Data of gene expression microarrays (GSE68468, GSE44076) and gene methylation microarrays (GSE29490, GSE17648) were downloaded from GEO database. Aberrantly methylated-DEGs were obtained by GEO2R. Functional and enrichment analyses of selected genes were performed using DAVID database...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28764718/comparative-analysis-of-the-egfr-her2-c-myc-and-met-variations-in-colorectal-cancer-determined-by-three-different-measures-gene-copy-number-gain-amplification-status-and-the-2013-asco-cap-guideline-criterion-for-her2-testing-of-breast-cancer
#19
Yoonjin Kwak, Sumi Yun, Soo Kyung Nam, An Na Seo, Kyu Sang Lee, Eun Shin, Heung-Kwon Oh, Duck Woo Kim, Sung Bum Kang, Woo Ho Kim, Hye Seung Lee
BACKGROUND: The purpose of this study was to explore gene copy number (GCN) variation of EGFR, HER2, c-MYC, and MET in patients with primary colorectal cancer (CRC). METHODS: Dual-colour silver-enhanced in situ hybridization was performed in tissue samples of 334 primary CRC patients. The amplification status (GCN ratio ≥2) and GCN gain (average GCN ≥4) data for the EGFR, HER2, c-MYC and MET genes were obtained. GCN variation was also assessed by the criterion of the 2013 ASCO/CAP guidelines for HER2 testing...
August 1, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28760399/tas-102-plus-bevacizumab-for-patients-with-metastatic-colorectal-cancer-refractory-to-standard-therapies-c-task-force-an-investigator-initiated-open-label-single-arm-multicentre-phase-1-2-study
#20
Yasutoshi Kuboki, Tomohiro Nishina, Eiji Shinozaki, Kentaro Yamazaki, Kohei Shitara, Wataru Okamoto, Takeshi Kajiwara, Toshihiko Matsumoto, Takahiro Tsushima, Nobuo Mochizuki, Shogo Nomura, Toshihiko Doi, Akihiro Sato, Atsushi Ohtsu, Takayuki Yoshino
BACKGROUND: In patients with heavily treated metastatic colorectal cancer, TAS-102-a combination of trifluridine and tipiracil-has shown a significant overall survival benefit compared with placebo. In preclinical models, TAS-102 plus bevacizumab has shown enhanced activity against colorectal cancer xenografts compared with that for either drug alone. In this phase 1/2 study, we assessed the activity and safety of TAS-102 plus bevacizumab. METHODS: We did this investigator-initiated, open-label, single-arm, multicentre, phase 1/2 trial of TAS-102 plus bevacizumab in four cancer centres in Japan...
September 2017: Lancet Oncology
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