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EGFR and colorectal cancer

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https://www.readbyqxmd.com/read/28531891/dual-inhibition-of-egfr-and-vegf-in-heavily-pretreated-patients-with-metastatic-colorectal-cancer
#1
Finn Ole Larsen, Alice Markussen, Dorte Nielsen, Bonnie Colville-Ebeling, Lene B Riis, Benny V Jensen
OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of combining irinotecan, bevacizumab, and cetuximab/panitumumab as a 4th-line treatment in patients with metastatic colorectal cancer. METHODS: All patients had KRAS wild-type metastatic colorectal cancer and had previously received fluoropyrimidine, oxaliplatin, irinotecan, and cetuximab/panitumumab in a 1st, 2nd, and 3rd line setting. Most patients had previously received bevacizumab as well...
May 23, 2017: Oncology
https://www.readbyqxmd.com/read/28513565/epidermal-growth-factor-receptor-cell-proliferation-signaling-pathways
#2
REVIEW
Ping Wee, Zhixiang Wang
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and breast cancer. Various mechanisms mediate the upregulation of EGFR activity, including common mutations and truncations to its extracellular domain, such as in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R and T790M mutations, or the exon 19 truncation...
May 17, 2017: Cancers
https://www.readbyqxmd.com/read/28510291/associations-between-rna-splicing-regulatory-variants-of-stemness-related-genes-and-racial-disparities-in-susceptibility-to-prostate-cancer
#3
Yanru Wang, Jennifer A Freedman, Hongliang Liu, Patricia G Moorman, Terry Hyslop, Daniel J George, Norman H Lee, Steven R Patierno, Qingyi Wei
Evidence suggests that cells with a stemness phenotype play a pivotal role in oncogenesis, and prostate cells exhibiting this phenotype have been identified. We used two genome-wide association study (GWAS) datasets of African descendants, from the Multiethnic/Minority Cohort Study of Diet and Cancer (MEC) and the Ghana Prostate Study, as well as two GWAS datasets of non-Hispanic whites, from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Breast and Prostate Cancer Cohort Consortium (BPC3), to analyze the associations between genetic variants of stemness-related genes and racial disparities in susceptibility to prostate cancer...
May 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28507280/molecular-dissection-of-effector-mechanisms-of-ras-mediated-resistance-to-anti-egfr-antibody-therapy
#4
Stefan Kasper, Henning Reis, Sophie Ziegler, Silke Nothdurft, Andre Mueller, Moritz Goetz, Marcel Wiesweg, Jeannette Phasue, Saskia Ting, Sarah Wieczorek, Anna Even, Karl Worm, Michael Pogorzelski, Sandra Breitenbuecher, Johannes Meiler, Andreas Paul, Tanja Trarbach, Kurt Werner Schmid, Frank Breitenbuecher, Martin Schuler
Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR), cetuximab and panitumumab, are a mainstay of metastatic colorectal cancer (mCRC) treatment. However, a significant number of patients suffer from primary or acquired resistance. RAS mutations are negative predictors of clinical efficacy of anti-EGFR antibodies in patients with mCRC. Oncogenic RAS activates the MAPK and PI3K/AKT pathways, which are considered the main effectors of resistance. However, the relative impact of these pathways in RAS-mutant CRC is less defined...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28486761/panitumumab-interaction-with-tas-102-leads-to-combinational-anticancer-effects-via-blocking-of-egfr-mediated-tumor-response-to-trifluridine
#5
Yuji Baba, Toshiya Tamura, Yoshihiko Satoh, Masamitsu Gotou, Hiroshi Sawada, Shunsuke Ebara, Kazunori Shibuya, Jumpei Soeda, Kazuhide Nakamura
Panitumumab is a monoclonal antibody developed against the human epidermal growth factor receptor (EGFR). TAS-102 is a novel chemotherapeutic agent containing trifluridine (FTD) as the active cytotoxic component. Both panitumumab and TAS-102 have been approved for the treatment of metastatic colorectal cancer. In this study, we revealed the mechanism underlying the anticancer effects of panitumumab/TAS-102 combination using preclinical models. Panitumumab/FTD co-treatment showed additive antiproliferative effects in LIM1215 and synergistic antiproliferative effects in SW48 colon cancer cells...
May 9, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28475674/no-benefit-from-the-addition-of-anti-egfr-antibody-in-all-right-sided-metastatic-colorectal-cancer
#6
Y Sunakawa, A Tsuji, M Fujii, W Ichikawa
No abstract text is available yet for this article.
May 5, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28473715/rationally-co-targeting-divergent-pathways-in-kras-wild-type-colorectal-cancers-by-canscript-technology-reveals-tumor-dependence-on-notch-and-erbb2
#7
Nilesh Brijwani, Misti Jain, Muthu Dhandapani, Farrah Zahed, Pragnashree Mukhopadhyay, Manjusha Biswas, Deepak Khatri, Vinod D Radhakrishna, Biswanath Majumder, Padhma Radhakrishnan, Saravanan Thiyagarajan
KRAS mutation status can distinguish between metastatic colorectal carcinoma (mCRC) patients who may benefit from therapies that target the epidermal growth factor receptor (EGFR), such as cetuximab. However, patients whose tumors harbor mutant KRAS (codons 12/13, 61 and 146) are often excluded from EGFR-targeted regimens, while other patients with wild type KRAS will sometimes respond favorably to these same drugs. These conflicting observations suggest that a more robust approach to individualize therapy may enable greater frequency of positive clinical outcome for mCRC patients...
May 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28463756/impact-of-braf-and-ras-mutations-on-first-line-efficacy-of-folfiri-plus-cetuximab-versus-folfiri-plus-bevacizumab-analysis-of-the-fire-3-aio-krk-0306-study
#8
S Stintzing, L Miller-Phillips, D P Modest, L Fischer von Weikersthal, T Decker, A Kiani, U Vehling-Kaiser, S-E Al-Batran, T Heintges, C Kahl, G Seipelt, F Kullmann, M Stauch, W Scheithauer, S Held, M Moehler, A Jagenburg, T Kirchner, A Jung, V Heinemann
BACKGROUND: RAS and BRAF mutations have been identified as negative prognostic factors in metastatic colorectal cancer. Efficacy of 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) plus bevacizumab in patients with RAS-mutant tumours needs to be further evaluated. Whether to treat patients with BRAF-mutant tumours with either bevacizumab or anti-epidermal growth factor receptor (EGFR) antibodies remains unclear. METHODS: Patients treated within the FIRE-3 trial were retrospectively tested for BRAF and RAS mutations using formalin fixated paraffin embedded (FFPE) tumour material applying pyrosequencing for KRAS and NRAS exon 2, 3 and 4 mutations as far as for BRAF mutations...
April 29, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28451421/role-of-ras-mutation-status-as-a-prognostic-factor-for-patients-with-advanced-colorectal-cancer-treated-with-first-line-chemotherapy-based-on-fluoropyrimidines-and-oxaliplatin-with-or-without-bevavizumab-a-retrospective-analysis
#9
Javier Garde Noguera, Eloisa Jantus-Lewintre, Mireia Gil-Raga, Elena Evgenyeva, Sonia Maciá Escalante, Antonio Llombart-Cussac, Carlos Camps Herrero
The role of Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) mutations as negative predictors for anti-epidermal growth factor receptor (EGFR) therapies in metastatic colorectal cancer (CRC) has been firmly established. However, whether the RAS mutation status plays a role as a biomarker for anti-vascular endothelial growth factor (VEGF) treatment remains controversial. Data from 93 CRC patients who received first-line cytotoxic chemotherapy with fluoropyrimidines and oxaliplatin, with or without bevacizumab, were analyzed...
March 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28447565/risk-factors-for-brain-metastases-in-patients-with-metastatic-colorectal-cancer
#10
Troels Dreier Christensen, Jesper Andreas Palshof, Finn Ole Larsen, Estrid Høgdall, Tim Svenstrup Poulsen, Per Pfeiffer, Benny Vittrup Jensen, Mette Karen Yilmaz, Ib Jarle Christensen, Dorte Nielsen
BACKGROUND: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict later risk of developing BM. Furthermore, we wished to estimate the incidence of BM in long-term surviving patients. MATERIAL AND METHODS: We conducted a retrospective study on a Danish multicenter cohort of patients with mCRC who received cetuximab and irinotecan (CetIri) as third-line treatment...
May 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28446505/clinical-features-and-outcomes-of-patients-with-colorectal-cancers-harboring-nras-mutations
#11
Andrea Cercek, Maria Ignez Braghiroli, Joanne F Chou, Jaclyn F Hechtman, Nancy E Kemeny, Leonard Saltz, Marinela Capanu, Rona Yaeger
Purpose: NRAS mutations are now routinely included in RAS testing prior to EGFR (epidermal growth factor receptor) inhibitor therapy for metastatic colorectal cancer (mCRC).  The clinical implications of NRAS mutation beyond lack of response to anti-EGFR therapy, however, are not known.  We undertook this study to determine the clinical features and treatment outcomes of patients with NRAS mutant mCRC.<br />Experimental Design: We reviewed clinical characteristics, concurrent mutations, and outcomes for all mCRC cases with NRAS mutations undergoing standard genotyping at our institution from 2008-2015...
April 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28445956/rhbdd1-upregulates-egfr-via-the-ap-1-pathway-in-colorectal-cancer
#12
Fei Miao, Mengmeng Zhang, Yuechao Zhao, Xiaolu Li, Rongyan Yao, Fan Wu, Rong Huang, Kai Li, Shiying Miao, Changwu Ma, Hongge Ju, Wei Song, Linfang Wang
Our previous study showed that RHBDD1 can activate the EGFR signaling pathway to promote colorectal cancer growth. In the present study, EGFR was decreased when RHBDD1 was knocked down or inactivated. Further analysis found that c-Jun and EGFR protein expression was decreased in RHBDD1 knockdown and inactivated cells. c-Jun overexpression in RHBDD1-inactivated cells rescued EGFR expression in a dose-dependent manner. RHBDD1 overexpression in RHBDD1-inactivated cells restored EGFR expression, but this effect was counteracted by c-Jun knockdown...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445743/egfr-targeted-micelles-containing-near-infrared-dye-for-enhanced-photothermal-therapy-in-colorectal-cancer
#13
Ying-Hsia Shih, Tsai-Yueh Luo, Ping-Fang Chiang, Cheng-Jung Yao, Wuu-Jyh Lin, Cheng-Liang Peng, Ming-Jium Shieh
The purpose of this research was to investigate the effectiveness of epidermal growth factor receptor (EGFR) targeted micelles loaded with IR-780 (Cetuximab/IR-780/micelles) for generating tumor targeting, multimodal images, and photothermal therapy (PTT). We initially studied the cellular uptake of these micelles using the HCT-116 and SW-620 cell lines. HCT-116 (high expression of EGFR) and SW-620 (low expression of EGFR) cell lines were used to examine biodistribution and antitumor effects of Cetuximab/IR-780/micelles...
April 23, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28436422/rational-design-of-non-resistant-targeted-cancer-therapies
#14
Francisco Martínez-Jiménez, John P Overington, Bissan Al-Lazikani, Marc A Marti-Renom
Drug resistance is one of the major problems in targeted cancer therapy. A major cause of resistance is changes in the amino acids that form the drug-target binding site. Despite of the numerous efforts made to individually understand and overcome these mutations, there is a lack of comprehensive analysis of the mutational landscape that can prospectively estimate drug-resistance mutations. Here we describe and computationally validate a framework that combines the cancer-specific likelihood with the resistance impact to enable the detection of single point mutations with the highest chance to be responsible of resistance to a particular targeted cancer therapy...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28435295/silencing-cdr1as-inhibits-colorectal-cancer-progression-through-regulating-microrna-7
#15
Wentao Tang, Meiling Ji, Guodong He, Liangliang Yang, Zhengchuan Niu, Mi Jian, Ye Wei, Li Ren, Jianmin Xu
An increasing number of studies have demonstrated that circular RNAs (circRNAs) can regulate gene expression through interacting with microRNAs. In this study, we analyzed the expression of antisense to CDR1as in colorectal cancer (CRC). CDR1as had a higher expression in CRC tissues compared to adjacent, normal mucosa and was positively associated with tumor size, T stage, lymph node metastasis, and poor overall survival (OS). Downregulation of CDR1as suppressed CRC cell proliferation and invasion and increased microRNA-7 (miR-7) expression...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28435294/patient-considerations-in-metastatic-colorectal-cancer-role-of-panitumumab
#16
REVIEW
Jane E Rogers
Epidermal growth factor receptor (EGFR) is overexpressed in many malignancies, including colorectal cancer (CRC), making EGFR an attractive treatment option. Panitumumab and cetuximab, monoclonal antibodies (mAbs) directed at EGFR, are both currently utilized in the management of metastatic CRC (mCRC). Through the development of these agents in mCRC, key issues surrounding each mAbs use have been revealed. These key issues include negative patient outcome avoidance when determining use, the economic burden with high-cost medication, predictive biomarkers, tumor location, patient geographic location, patient quality of life, and the prevention of debilitating adverse effects...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28432610/left-versus-right-does-location-matter-for-refractory-metastatic-colorectal-cancer-patients-in-phase-1-clinical-trials
#17
Sukeshi Patel Arora, Norma S Ketchum, Joel Michalek, Jonathon Gelfond, Devalingam Mahalingam
PURPOSE: Location of the primary tumor is prognostic and predictive of efficacy with VEGF-inhibitors (I) versus EGFR-I given first-line to metastatic colorectal cancer (mCRC) patients. However, little is known regarding the effect of location on prognosis and prediction in refractory mCRC. We assessed the efficacy of VEGF-I and EGFR-I in regards to location of the primary tumor in patients with refractory mCRC enrolled in early phase studies. METHODS: A historical cohort analysis of mCRC patients, including 44 phase I trials our institution, from March 2004 to September 2012...
April 22, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28432289/simultaneous-detection-of-egfr-and-vegf-in-colorectal-cancer-using-fluorescence-raman-endoscopy
#18
Yong-Il Kim, Sinyoung Jeong, Kyung Oh Jung, Myung Geun Song, Chul-Hee Lee, Seock-Jin Chung, Ji Yong Park, Myeong Geun Cha, Sung Gun Lee, Bong-Hyun Jun, Yun-Sang Lee, Do Won Hwang, Hyewon Youn, Keon Wook Kang, Yoon-Sik Lee, Dae Hong Jeong, Dong Soo Lee
Fluorescence endomicroscopy provides quick access to molecular targets, while Raman spectroscopy allows the detection of multiple molecular targets. Using a simultaneous fluorescence-Raman endoscopic system (FRES), we herein demonstrate its potential in cancer diagnosis in an orthotopically induced colorectal cancer (CRC) xenograft model. In the model, epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) were targeted with antibody-conjugated fluorescence and surface-enhanced Raman scattering (F-SERS) dots...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424201/pik3ca-mutations-contribute-to-acquired-cetuximab-resistance-in-metastatic-colorectal-cancer-patients
#19
Jian Ming Xu, Yan Wang, You-Liang Wang, Yan Wang, Tao Liu, Ming Ni, Man-Sheng Li, Li Lin, Fei-Jiao Ge, Chun Gong, Jun-Yan Gu, Ru Jia, He-Fei Wang, Yu Ling Chen, Rong-Rui Liu, Chuan-Hua Zhao, Zhao-Li Tan, Yang Jin, Yunping Zhu, Shuji Ogino, Zhi Rong Qian
<p>Mutations in KRAS are considered to be the main drivers of acquired resistance to epidermal growth factor receptor (EGFR) blockade in patients with metastatic colorectal cancer (mCRC). However, the potential roles of other genes downstream of the EGFR signaling pathway in conferring acquired resistance has not been extensively investigated.</p> <br /><br />Experimental Design: <p>Using circulating tumor DNA (ctDNA) from patients with mCRC and with acquired cetuximab resistance, we developed a targeted amplicon ultra-deep sequencing method to screen for low-abundance somatic mutations in a panel of genes that encode components of the EGFR signaling pathway...
April 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28423516/the-addition-of-celecoxib-improves-the-antitumor-effect-of-cetuximab-in-colorectal-cancer-role-of-egfr-ras-foxm1-%C3%AE-catenin-signaling-axis
#20
Araceli Valverde, Jon Peñarando, Amanda Cañas, Laura M López-Sánchez, Francisco Conde, Silvia Guil-Luna, Vanessa Hernández, Carlos Villar, Cristina Morales-Estévez, Juan de la Haba-Rodríguez, Enrique Aranda, Antonio Rodríguez-Ariza
Here we showed that the addition of the COX-2 inhibitor celecoxib improved the antitumor efficacy in colorectal cancer (CRC) of the monoclonal anti-EGFR antibody cetuximab. The addition of celecoxib augmented the efficacy of cetuximab to inhibit cell proliferation and to induce apoptosis in CRC cells. Moreover, the combination of celecoxib and cetuximab was more effective than either treatment alone in reducing the tumor volume in a mouse xenograft model. The combined treatment enhanced the inhibition of EGFR signaling and altered the subcellular distribution of β-catenin...
March 28, 2017: Oncotarget
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