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EGFR and colorectal cancer

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https://www.readbyqxmd.com/read/28819429/map2k1-mutation-in-colorectal-cancer-patients-therapeutic-challenge-using-patient-derived-tumor-cell-lines
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
July 28, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28759012/berberine-inhibits-colitis-associated-tumorigenesis-via-suppressing-inflammatory-responses-and-the-consequent-egfr-signaling-involved-tumor-cell-growth
#9
Dandan Li, Youyu Zhang, Kun Liu, Yujie Zhao, Beibei Xu, Liang Xu, Li Tan, Yuan Tian, Cunxi Li, Wenqing Zhang, Hanwei Cao, Yan-Yan Zhan, Tianhui Hu
The anti-inflammatory and anti-tumor effects of berberine, a traditional Chinese medicine, were separately discovered in pathological intestinal tissues. However, whether the anti-inflammatory effect of berberine contributes to its anti-tumor effect on colitis-associated colorectal cancer (CACRC) remains unknown. In the present study, we found that berberine effectively inhibited colitis-associated tumorigenesis and colonic epithelium hyperproliferation in dextran sulfate sodium (DSS)-treated Apc(Min/+) mice...
July 31, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28752777/anti-egfr-monoclonal-antibody-panitumumab-for-the-treatment-of-patients-with-metastatic-colorectal-cancer-an-overview-of-current-practice-and-future-perspectives
#10
Francesca Battaglin, Vincenzo Dadduzio, Francesca Bergamo, Chiara Manai, Marta Schirripa, Sara Lonardi, Vittorina Zagonel, Fotios Loupakis
Targeted agents alone or in combination with chemotherapy are current standard of treatment for metastatic colorectal cancer (mCRC). Panitumumab is a fully human monoclonal antibody which inhibits the epidermal growth factor receptor (EGFR). It is currently approved in combination with chemotherapy in first- and second-line and as a monotherapy in chemorefractory patients. RAS gene mutations confer resistance to anti-EGFR agents; thus, panitumumab is restricted to the treatment of RAS wild-type (WT) tumors...
July 28, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28747067/ras-mutation-prevalence-among-patients-with-metastatic-colorectal-cancer-a-meta-analysis-of-real-world-data
#11
George Kafatos, Daniela Niepel, Kimberley Lowe, Sophie Jenkins-Anderson, Hal Westhead, Tamer Garawin, Zuzana Traugottová, Antonios Bilalis, Edit Molnar, Jozsef Timar, Erika Toth, Nikolaos Gouvas, George Papaxoinis, Samuel Murray, Nadia Mokhtar, Hana Vosmikova, Pavel Fabian, Alena Skalova, Piotr Wójcik, Andrzej Tysarowski, Mario Barugel, J Han van Krieken, Jörg Trojan
AIM: A confirmed wild-type RAS tumor status is commonly required for prescribing anti-EGFR treatment for metastatic colorectal cancer. This noninterventional, observational research project estimated RAS mutation prevalence from real-world sources. MATERIALS & METHODS: Aggregate RAS mutation data were collected from 12 sources in three regions. Each source was analyzed separately; pooled prevalence estimates were then derived from meta-analyses. RESULTS: The pooled RAS mutation prevalence from 4431 tumor samples tested for RAS mutation status was estimated to be 43...
July 27, 2017: Biomarkers in Medicine
https://www.readbyqxmd.com/read/28740573/telomere-length-regulation-through-epidermal-growth-factor-receptor-signaling-in-cancer
#12
REVIEW
Titto Augustine, Radhashree Maitra, Sanjay Goel
Length of the telomere (TL), a structure at the tip of chromosome that protects and ensures stability, is determined by multi-protein complexes such as telosome/shelterin and telomerase. Earlier studies from our laboratory show that longer TL has potential to be positive predictive biomarker of clinical outcome to anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy in patients with KRAS WT metastatic colorectal cancer. Although there is extensive literature suggesting the role of shelterin and telomerase, not much literature exists that describes the role of EGFR and KRAS pathway in regulating TL...
May 2017: Genes & Cancer
https://www.readbyqxmd.com/read/28738328/a-novel-role-for-mir-520a-3p-in-regulating-egfr-expression-in-colorectal-cancer
#13
Rui Zhang, Rui Liu, Chang Liu, Yahan Niu, Jianguo Zhang, Baoliang Guo, Chen-Yu Zhang, Jing Li, Jie Yang, Xi Chen
BACKGROUND/AIMS: MicroRNAs (miRNAs) have been consistently demonstrated to be involved in colorectal cancer as either tumour oncogenes or tumour suppressors. However, the detailed role of miR-520a-3p in colorectal cancer remains poorly understood. METHODS: Quantitative RT-PCR and western blotting assays were used to measure miR-520a-3p and EGFR expression levels in colorectal cancer tissues, respectively. Luciferase reporter assay was employed to validate the direct targeting of EGFR by miR-520a-3p...
July 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28738235/treatment-decisions-in-metastatic-colorectal-cancer-beyond-first-and-second-line-combination-therapies
#14
REVIEW
A Vogel, R D Hofheinz, S Kubicka, D Arnold
Median overall survival (OS) of patients with metastatic colorectal cancer (mCRC) has reached up to 30months in recent clinical trials of first line therapies. Following disease progression after the standard in both, 1st and 2nd line, combination chemotherapy with monoclonal antibodies, many patients maintain a good performance status and a significant proportion is motivated to undergo further therapy. Choices of treatment beyond the second line setting for mCRC are therefore becoming increasingly important...
May 4, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28736637/primary-and-acquired-resistance-to-biologic-therapies-in-gastrointestinal-cancers
#15
REVIEW
Sam J Lubner, Nataliya V Uboha, Dustin A Deming
Improvements in the understanding of cancer biology have led to therapeutic advances in the treatment of gastrointestinal cancers. Drugs which target the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways have led the way in colon cancer. Monoclonal antibodies (mAbs) such as bevacizumab, ramucirumab, cetuximab, and panitumumab, have improved progression free survival and overall survival (OS) for colorectal cancers and were quickly adopted. Human epidermal growth factor receptor 2 (HER2) has demonstrated significant benefit for gastroesophageal cancers and in the setting of HER2 amplification, trastuzumab in combination with chemotherapy has become the standard of care...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736628/predictive-and-prognostic-biomarkers-in-personalized-gastrointestinal-cancer-treatment
#16
REVIEW
Helena Verdaguer, Tamara Saurí, Teresa Macarulla
Biomarkers play an important role in the detection and management of cancer patients. In gastrointestinal cancer, there is increasing interest in their development and validation according to specific tumor type. Prognostic biomarkers enable identification of patients with a more aggressive tumor evolution, while predictive biomarkers permit the identification of patients with a higher probability of responding or not to a specific treatment. Several biomarkers are currently widely employed in gastrointestinal cancers...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736627/personalized-and-precision-medicine-integrating-genomics-into-treatment-decisions-in-gastrointestinal-malignancies
#17
REVIEW
Trang H Au, Kai Wang, David Stenehjem, Ignacio Garrido-Laguna
The advent of next generation sequencing (NGS) technologies has advanced our understanding of the intrinsic biology of different gastrointestinal (GI) tumor types. The use of novel, more efficient sequencing platforms has improved turnaround times of sequencing results. This is providing real time opportunities to put precision medicine to the test. A number of early phase clinical trials are testing targeted therapies in unique molecularly characterized subsets of patients (baskets). While basket studies are gaining momentum, treatment failures serve to remind us that shifting from a histology-driven to a histology-agnostic approach is unlikely to be a failure-free strategy for a number of tumor types as recently learnt from vemurafenib failure in BRAF mutated metastatic colorectal cancer (mCRC)...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28716720/met-signaling-mediates-intestinal-crypt-villus-development-regeneration-and-adenoma-formation-and-is-promoted-by-stem-cell-cd44-isoforms
#18
Sander P J Joosten, Jurrit Zeilstra, Harmen van Andel, R Clinton Mijnals, Joost Zaunbrecher, Annet A M Duivenvoorden, Marc van de Wetering, Hans Clevers, Marcel Spaargaren, Steven T Pals
BACKGROUND & AIMS: Resistance of metastatic human colorectal cancer cells to drugs that block epidermal growth factor receptor (EGFR) signaling could be caused by aberrant activity of other receptor tyrosine kinases, activating overlapping signaling pathways. One of these receptor tyrosine kinases could be MET, the receptor for hepatocyte growth factor (HGF). We investigated how MET signaling, and its interaction with CD44 (a putative MET co-receptor regulated by Wnt signaling and highly expressed by intestinal stem cells [ISCs] and adenomas) affects intestinal homeostasis, regeneration, and adenoma formation in mini-gut organoids and mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28714940/non-coding-rnas-as-predictive-biomarkers-to-current-treatment-in-metastatic-colorectal-cancer
#19
REVIEW
Ingrid Garajová, Manuela Ferracin, Elisa Porcellini, Andrea Palloni, Francesca Abbati, Guido Biasco, Giovanni Brandi
The onset and selection of resistant clones during cancer treatment with chemotherapy or targeted therapy is a major issue in the clinical management of metastatic colorectal cancer patients. It is possible that a more personalized treatment selection, using reliable response-to-therapy predictive biomarkers, could lead to an improvement in the success rate of the proposed therapies. Although the process of biomarker selection and validation could be a long one, requiring solid statistics, large cohorts and multicentric validations, non-coding RNAs (ncRNAs) and in particular microRNAs, proved to be extremely promising in this field...
July 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28712102/precision-medicine-in-metastatic-colorectal-cancer-relevant-carcinogenic-pathways-and-targets-part-2-approaches-beyond-first-line-therapy-and-novel-biologic-agents-under-investigation
#20
REVIEW
Benjamin A Weinberg, Marion L Hartley, Mohamed E Salem
A frequent quandary for oncologists is the selection of chemotherapy and biologic therapy for patients with metastatic colorectal cancer in second-line and higher treatment settings. While not approved by the US Food and Drug Administration (FDA) in the first-line setting, the vascular endothelial growth factor (VEGF)-targeting agents ziv-aflibercept and ramucirumab are appropriate treatment options in the second-line setting, as is continuation of first-line bevacizumab. Tumor RAS mutational status is helpful to determine which patients may benefit from epidermal growth factor receptor (EGFR)-directed therapies, and other novel biomarkers (BRAF, HER2, and mismatch repair deficiency) allow us to select patients who may benefit from biologic therapies that are FDA-approved for other malignancies...
July 15, 2017: Oncology (Williston Park, NY)
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