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https://www.readbyqxmd.com/read/28230863/oncogenic-role-of-rab-escort-protein-1-through-egfr-and-stat3-pathway
#1
Un-Jung Yun, Jee Young Sung, Seog-Yun Park, Sang-Kyu Ye, Jaegal Shim, Jae-Seon Lee, Masahiko Hibi, Young-Ki Bae, Yong-Nyun Kim
Rab escort protein-1 (REP1) is linked to choroideremia (CHM), an X-linked degenerative disorder caused by mutations of the gene encoding REP1 (CHM). REP1 mutant zebrafish showed excessive cell death throughout the body, including the eyes, indicating that REP1 is critical for cell survival, a hallmark of cancer. In the present study, we found that REP1 is overexpressed in human tumor tissues from cervical, lung, and colorectal cancer patients, whereas it is expressed at relatively low levels in the normal tissue counterparts...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28223233/unravelling-the-pharmacologic-opportunities-and-future-directions-for-targeted-therapies-in-gastro-intestinal-cancers-part-1-gi-carcinomas
#2
REVIEW
Cindy Neuzillet, Benoît Rousseau, Hemant Kocher, Philippe Bourget, Christophe Tournigand
Until the 1990s, cytotoxic chemotherapy has been the cornerstone of medical therapy for gastrointestinal (GI) cancers. Better understanding of the molecular biology of cancer cell has led to the therapeutic revolution of targeted therapies, i.e. monoclonal antibodies or small molecule inhibitors directed against proteins that are specifically overexpressed or mutated in cancer cells. These agents being more specific to cancer cells were expected to be less toxic than cytotoxic agents. Targeted agents have provided clinical benefit in many GI cancer types...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28220486/cetuximab-plus-irinotecan-versus-panitumumab-in-patients-with-refractory-metastatic-colorectal-cancer-in-ontario-canada
#3
Katarzyna J Jerzak, Scott Berry, Yoo-Joung Ko, Craig Earle, Kelvin K W Chan
The addition of irinotecan to an EGFR antibody has previously been shown to improve tumor response rate and time to progression but not overall survival (OS) for refractory metastatic colorectal cancer (mCRC). We assessed the "real world" effectiveness and toxicity of the combination versus monotherapy. In Ontario, Canada universal public funding is available for either cetuximab plus irinotecan (Cmab+I) combination therapy or panitumumab (Pmab) monotherapy, only in patients with refractory non-mutated RAS mCRC...
February 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28220124/in-vivo-efficacy-of-umbilical-cord-blood-stem-cell-derived-nk-cells-in-the-treatment-of-metastatic-colorectal-cancer
#4
John P Veluchamy, Silvia Lopez-Lastra, Jan Spanholtz, Fenna Bohme, Nina Kok, Daniëlle A M Heideman, Henk M W Verheul, James P Di Santo, Tanja D de Gruijl, Hans J van der Vliet
Therapeutic monoclonal antibodies against the epidermal growth factor receptor (EGFR) act by inhibiting EGFR downstream signaling and by eliciting a natural killer (NK) cell-mediated antitumor response. The IgG1 mAb cetuximab has been used for treatment of RAS(wt) metastatic colorectal cancer (mCRC) patients, showing limited efficacy. In the present study, we address the potential of adoptive NK cell therapy to overcome these limitations investigating two allogeneic NK cell products, i.e., allogeneic activated peripheral blood NK cells (A-PBNK) and umbilical cord blood stem cell-derived NK cells (UCB-NK)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28219002/molecular-testing-for-gastrointestinal-cancer
#5
Hye Seung Lee, Woo Ho Kim, Yoonjin Kwak, Jiwon Koh, Jeong Mo Bae, Kyoung-Mee Kim, Mee Soo Chang, Hye Seung Han, Joon Mee Kim, Hwal Woong Kim, Hee Kyung Chang, Young Hee Choi, Ji Y Park, Mi Jin Gu, Min Jin Lhee, Jung Yeon Kim, Hee Sung Kim, Mee-Yon Cho
With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wild-type RAS (KRAS and NRAS exon 2-4). A BRAF mutation is required for predicting poor prognosis...
February 19, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28214977/braf-mutated-colorectal-cancer-what-is-the-optimal-strategy-for-treatment
#6
REVIEW
Romain Cohen, Pascale Cervera, Magali Svrcek, Anna Pellat, Chantal Dreyer, Aimery de Gramont, Thierry André
The BRAF activating mutation, harbored by approximately 10% of colorectal cancers (CRC), confers dramatic prognosis to advanced diseases. In early-stage setting, the identification of the BRAF mutation does not impact the therapeutic decision. Yet, the BRAF mutation could be considered as a stratification factor in adjuvant trials, because of its prognostic impact after relapse. Moreover, both BRAF mutation and mismatch repair (MMR) statuses should be determined in all CRC to help identify sporadic tumors versus Lynch syndrome-related tumors...
February 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28213365/fda-approval-summary-tas-102
#7
Leigh Marcus, Steven J Lemery, Sachia Khasar, Emily Wearne, Whitney S Helms, Weishi Yuan, Kun He, Xianhua Cao, Jingyu Yu, Hong Zhao, Yaning Wang, Olen Stephens, Erika Englund, Rajiv Agarwal, Patricia Keegan, Richard Pazdur
FDA approved TAS-102 (Lonsurf, Taiho Oncology, Inc.) for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. In an international, multicenter, double-blinded, placebo-controlled trial (TPU-TAS-102-301, herein referred to as RECOURSE), 800 patients with previously treated mCRC were randomly allocated (2:1) to receive either TAS-102 35mg/m2 orally twice daily after meals on Days 1-5 and 8-12 of each 28-day cycle (n=534) or matching placebo (n=266)...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28199979/atm-mutations-and-e-cadherin-expression-define-sensitivity-to-egfr-targeted-therapy-in-colorectal-cancer
#8
Anna-Lena Geißler, Miriam Geißler, Daniel Kottmann, Lisa Lutz, Christiane D Fichter, Ralph Fritsch, Britta Weddeling, Frank Makowiec, Martin Werner, Silke Lassmann
EGFR-targeted therapy is a key treatment approach in patients with RAS wildtype metastatic colorectal cancers (CRC). Still, also RAS wildtype CRC may be resistant to EGFR-targeted therapy, with few predictive markers available for improved stratification of patients. Here, we investigated response of 7 CRC cell lines (Caco-2, DLD1, HCT116, HT29, LS174T, RKO, SW480) to Cetuximab and correlated this to NGS-based mutation profiles, EGFR promoter methylation and EGFR expression status as well as to E-cadherin expression...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197371/prophylactic-vaccination-targeting-erbb3-decreases-polyp-burden-in-a-mouse-model-of-human-colorectal-cancer
#9
David J Bautz, Ang T Sherpa, David W Threadgill
Prophylactic vaccination is typically utilized for the prevention of communicable diseases such as measles and influenza but, with the exception of vaccines to prevent cervical cancer, is not widely used as a means of preventing or reducing the incidence of cancer. Here, we utilize a peptide-based immunotherapeutic approach targeting ERBB3, a pseudo-kinase member of the EGFR/ERBB family of receptor tyrosine kinases, as a means of preventing occurrence of colon polyps. Administration of the peptide resulted in a significant decrease in the development of intestinal polyps in C57BL/6J-Apc(Min) mice, a model of familial adenomatous polyposis (FAP)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28186126/molecular-dissection-of-colorectal-cancer-in-pre-clinical-models-identifies-biomarkers-predicting-sensitivity-to-egfr-inhibitors
#10
Moritz Schütte, Thomas Risch, Nilofar Abdavi-Azar, Karsten Boehnke, Dirk Schumacher, Marlen Keil, Reha Yildiriman, Christine Jandrasits, Tatiana Borodina, Vyacheslav Amstislavskiy, Catherine L Worth, Caroline Schweiger, Sandra Liebs, Martin Lange, Hans-Jörg Warnatz, Lee M Butcher, James E Barrett, Marc Sultan, Christoph Wierling, Nicole Golob-Schwarzl, Sigurd Lax, Stefan Uranitsch, Michael Becker, Yvonne Welte, Joseph Lewis Regan, Maxine Silvestrov, Inge Kehler, Alberto Fusi, Thomas Kessler, Ralf Herwig, Ulf Landegren, Dirk Wienke, Mats Nilsson, Juan A Velasco, Pilar Garin-Chesa, Christoph Reinhard, Stephan Beck, Reinhold Schäfer, Christian R A Regenbrecht, David Henderson, Bodo Lange, Johannes Haybaeck, Ulrich Keilholz, Jens Hoffmann, Hans Lehrach, Marie-Laure Yaspo
Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I-IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling >4,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28185757/molecular-biomarkers-for-the-evaluation-of-colorectal-cancer-guideline-from-the-american-society-for-clinical-pathology-college-of-american-pathologists-association-for-molecular-pathology-and-american-society-of-clinical-oncology
#11
REVIEW
Antonia R Sepulveda, Stanley R Hamilton, Carmen J Allegra, Wayne Grody, Allison M Cushman-Vokoun, William K Funkhouser, Scott E Kopetz, Christopher Lieu, Noralane M Lindor, Bruce D Minsky, Federico A Monzon, Daniel J Sargent, Veena M Singh, Joseph Willis, Jennifer Clark, Carol Colasacco, R Bryan Rumble, Robyn Temple-Smolkin, Christina B Ventura, Jan A Nowak
OBJECTIVES: To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens. METHODS: The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC...
February 2, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28183254/metastatic-colorectal-cancer-role-of-target-therapies-and-future-perspectives
#12
Anna Nappi, Massimiliano Berretta, Carmela Romano, Salvatore Tafuto, Antonino Cassata, Rossana Casaretti, Lucrezia Silvestro, Chiara De Divitiis, Lara Alessandrini, Francesco Fiorica, Alessandro Ottaiano, Guglielmo Nasti
Today, we are experiencing a real cultural revolution in the therapeutic approach to cancer of the colon - rectum, that, by orphan disease, it is now becoming an important paradigm of scientific innovations and concepts. Survival of patients with metastatic colorectal cancer (m-CRC) has been significantly improved with the introduction of the monoclonal antibodies that have as target the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). Novel agents such as aflibercept and regorafenib have recently been approved...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28183250/the-role-of-target-therapy-in-the-treatment-of-gastrointestinal-non-colorectal-cancers-clinical-impact-and-cost-consideration
#13
Massimiliano Berretta, Raffaele Di Francia, Chiara De Diviitis, Guglielmo Nasti, Vincenzo Canzonieri, Michele Caraglia, Gaetano Facchini, Umberto Tirelli
Gastrointestinal (GI) tumors are a leading cause of cancer-related deaths in the world. In fact, gastric cancer (GC) is the third cause of cancer deaths, whereas aesophageal neoplasm is the eighth most common cancer worldwide and its incidence, especially adenocarcinoma type, is continuously increasing. Also Hepatocellular carcinoma, Cholangiocarcinoma and pancreatic cancer represent a very interesting model to multidisciplinary approach and recently new drugs are used in their treatment. Currently, new clinical trials are designed including classic chemotherapy in association with either small molecule inhibitors (i...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28183047/gene-expression-changes-in-colon-tissues-from-colorectal-cancer-patients-following-the-intake-of-an-ellagitannin-containing-pomegranate-extract-a-randomized-clinical-trial
#14
María A Nuñez-Sánchez, Antonio González-Sarrías, Rocío García-Villalba, Tamara Monedero-Saiz, Noelia V García-Talavera, María B Gómez-Sánchez, Carmen Sánchez-Álvarez, Ana M García-Albert, Francisco J Rodríguez-Gil, Miguel Ruiz-Marín, Francisco A Pastor-Quirante, Francisco Martínez-Díaz, Francisco A Tomás-Barberán, Juan Carlos Espín, María-Teresa García-Conesa
The clinical evidence of dietary polyphenols as colorectal cancer (CRC) chemopreventive compounds is very weak. Verification in humans of tissue-specific molecular regulation by the intake of polyphenols requires complex clinical trials that allow for the procurement of sufficient pre- and postsupplementation tissue samples. Ellagitannins (ETs), ellagic acid (EA) and their gut microbiota-derived metabolites, the urolithins, modify gene expression in colon normal and cancer cultured cells. We conducted here the first clinical trial with 35 CRC patients daily supplemented with 900 mg of an ET-containing pomegranate extract (PE) and evaluated the expression of various CRC-related genes in normal and cancerous colon tissues before (biopsies) and after (surgical specimens) 5-35 days of supplementation...
January 27, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28182330/heat-shock-protein-27-hsp27-hspb1-is-synthetic-lethal-to-cells-with-oncogenic-activation-of-met-egfr-and-braf
#15
John David Konda, Martina Olivero, Daniele Musiani, Simona Lamba, Maria Flavia Di Renzo
The small Heat Shock Protein of 27 KDa (HSP27) is highly expressed in many cancers and is associated with aggressive tumor behaviour, metastasis, poor prognosis and resistance to chemotherapy. We aimed at assessing the role of HSP27 in modulating responses to target therapies. We selected several oncogene-addicted cancer cell lines, which undergo either cell cycle blockade or cell death in response to agents that target the specific oncogene. Surprisingly, HSP27 suppression alone resulted in the apoptotic death of MET-addicted EBC-1 lung cancer cells, EGFR-addicted colorectal carcinoma DiFi cells and BRAF-addicted colorectal carcinoma COLO205 and OXCO-1 and melanoma COLO741 cells, all of which also undergo death when treated with the specific targeted agent...
February 9, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28178681/molecular-profiling-of-metastatic-colorectal-tumors-using-next-generation-sequencing-a-single-institution-experience
#16
Jun Gong, May Cho, Marvin Sy, Ravi Salgia, Marwan Fakih
BACKGROUND: Recent molecular characterization of colorectal tumors has identified several molecular alterations of interest that are considered targetable in metastatic colorectal cancer (mCRC). METHODS: We conducted a single-institution, retrospective study based on comprehensive genomic profiling of tumors from 138 patients with mCRC using next-generation sequencing (NGS) via FoundationOne. RESULTS: Overall, RAS mutations were present in 51...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28174233/circular-rna-cirs-7-a-promising-prognostic-biomarker-and-a-potential-therapeutic-target-in-colorectal-cancer
#17
Wenhao Weng, Qing Wei, Shusuke Toden, Kazuhiro Yoshida, Takeshi Nagasaka, Toshiyoshi Fujiwara, Sanjun Cai, Huanlong Qin, Yanlei Ma, Ajay Goel
PURPOSE: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Recently, a novel circular RNA, ciRS-7, was proposed to be a potential miR-7 sponge. Since miR-7 regulates the expression of several important drivers of CRC, we analyzed the clinical significance of ciRS-7 in CRC patients. EXPERIMENTAL DESIGN: Initially, we evaluated the expression levels of ciRS-7 in a training cohort comprising of 153 primary CRC tissues and 44 matched normal mucosae...
February 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28173629/enhanced-dependency-of-kras-mutant-colorectal-cancer-cells-on-rad51-dependent-homologous-recombination-repair-identified-from-genetic-interactions-in-saccharomyces-cerevisiae
#18
Murugan Kalimutho, Amanda L Bain, Bipasha Mukherjee, Purba Nag, Devathri M Nanayakkara, Sarah K Harten, Janelle L Harris, Goutham Narayanan Subramanian, Debottam Sinha, Senji Shirasawa, Sriganesh Srihari, Sandeep Burma, Kum Kum Khanna
Activating KRAS mutations drive colorectal cancer tumorigenesis and influence response to anti-EGFR targeted therapy. Despite recent advances in understanding Ras signaling biology and the revolution in therapies for melanoma using BRAF inhibitors, no targeted agents have been effective in KRAS mutant cancers, mainly due to activation of compensatory pathways. Here, by leveraging the largest synthetic lethal genetic interactome in yeast, we identify that KRAS-mutated colorectal cancer cells have augmented homologous recombination repair (HRR) signaling...
February 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28170370/development-of-a-gene-panel-for-next-generation-sequencing-of-clinically-relevant-mutations-in-cell-free-dna-from-cancer-patients
#19
Umberto Malapelle, Clara Mayo de-Las-Casas, Danilo Rocco, Monica Garzon, Pasquale Pisapia, Nuria Jordana-Ariza, Maria Russo, Roberta Sgariglia, Caterina De Luca, Francesco Pepe, Alejandro Martinez-Bueno, Daniela Morales-Espinosa, María González-Cao, Niki Karachaliou, Santiago Viteri Ramirez, Claudio Bellevicine, Miguel Angel Molina-Vila, Rafael Rosell, Giancarlo Troncone
BACKGROUND: When tumour tissue is unavailable, cell-free DNA (cfDNA)can serve as a surrogate for genetic analyses. Because mutated alleles in cfDNA are usually below 1%, next-generation sequencing (NGS)must be narrowed to target only clinically relevant genes. In this proof-of-concept study, we developed a panel to use in ultra-deep sequencing to identify such mutations in cfDNA. METHODS: Our panel ('SiRe') covers 568 mutations in six genes (EGFR, KRAS, NRAS, BRAF, cKIT and PDGFRα)involved in non-small-cell lung cancer (NSCLC), gastrointestinal stromal tumour, colorectal carcinoma and melanoma...
February 7, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28166195/detecting-intratumoral-heterogeneity-of-egfr-activity-by-liposome-based-in-vivo-transfection-of-a-fluorescent-biosensor
#20
G Weitsman, N J Mitchell, R Evans, A Cheung, T L Kalber, R Bofinger, G O Fruhwirth, M Keppler, Z V F Wright, P R Barber, P Gordon, T de Koning, W Wulaningsih, K Sander, B Vojnovic, S Ameer-Beg, M Lythgoe, J N Arnold, E Årstad, F Festy, H C Hailes, A B Tabor, T Ng
Despite decades of research in the epidermal growth factor receptor (EGFR) signalling field, and many targeted anti-cancer drugs that have been tested clinically, the success rate for these agents in the clinic is low, particularly in terms of the improvement of overall survival. Intratumoral heterogeneity is proposed as a major mechanism underlying treatment failure of these molecule-targeted agents. Here we highlight the application of fluorescence lifetime microscopy (FLIM)-based biosensing to demonstrate intratumoral heterogeneity of EGFR activity...
February 6, 2017: Oncogene
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