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EGFR and colorectal cancer

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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
#1
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
#2
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
#3
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)
https://www.readbyqxmd.com/read/28712098/precision-medicine-in-metastatic-colorectal-cancer-relevant-carcinogenic-pathways-and-targets-part-1-biologic-therapies-targeting-the-epidermal-growth-factor-receptor-and-vascular-endothelial-growth-factor
#4
REVIEW
Benjamin A Weinberg, Marion L Hartley, Mohamed E Salem
The survival of patients with metastatic colorectal cancer has improved dramatically in recent years, with overall survival exceeding 3 years in large randomized clinical trials. There are now several treatment options for patients with metastatic colorectal cancer. In addition to chemotherapy backbones utilizing fluoropyrimidine, oxaliplatin, and irinotecan combinations, biologic agents that target specific oncogenic pathways have contributed to the improved survival observed in this patient population. This class of medications includes epidermal growth factor receptor (EGFR)-targeted drugs (cetuximab and panitumumab) and vascular endothelial growth factor (VEGF)-targeted therapies (bevacizumab, ramucirumab, ziv-aflibercept, and regorafenib)...
July 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28711984/clarithromycin-co-administration-does-not-increase-irinotecan-cpt-11-toxicity-in-colorectal-cancer-patients
#5
Katsuya Makihara, Sayaka Nakamura, Kazuyo Miyagi, Hiroyuki Ueno, Izumi Nakata
PURPOSE: Irinotecan (CPT-11) is used to treat advanced colorectal cancer. The drug is activated by carboxylesterases and rendered inactive by CYP3A4. Recently, the efficacy of combining CPT-11 and anti-epidermal growth factor receptor (EGFR) agents was confirmed in patients with KRAS wild-type metastatic colorectal cancer. Clarithromycin (CAM) is a strong CYP3A inhibitor often used to prevent rash associated with anti-EGFR therapy. The objective of this study was to evaluate the risk of increased neutropenia and diarrhea in combining CPT-11 and CAM...
July 15, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28708103/pharmacogenomics-of-targeted-agents-for-personalization-of-colorectal-cancer-treatment
#6
REVIEW
Alessia Bignucolo, Elena De Mattia, Erika Cecchin, Rossana Roncato, Giuseppe Toffoli
The use of targeted agents in the treatment of metastatic colorectal cancer (CRC) has improved patient outcomes. Anti-epidermal growth factor receptor (anti-EGFR) agents (cetuximab and panitumumab) and antiangiogenic molecules (bevacizumab, regorafeninb, ramucirumab, and aflibercept) have been successfully integrated into clinical practice. Other drugs have been designed to target additional deregulated pathways in CRC, such as MAPK (mitogen-activated protein kinase)/PI3K-AKT (phosphatidylinositol-3-kinase-AKT serine/threonine kinase)/mTOR (mammalian target of rapamycin), HER-2 and 3 ( human epidermal growth factor receptor-2 and -3), and BRAF...
July 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28702704/ezrin-orchestrates-signal-transduction-in-airway-cells
#7
Lei-Miao Yin, Ting-Ting Duan, Luis Ulloa, Yong-Qing Yang
Ezrin is a critical structural protein that organizes receptor complexes and orchestrates their signal transduction. In this study, we review the ezrin-meditated regulation of critical receptor complexes, including the epidermal growth factor receptor (EGFR), CD44, vascular cell adhesion molecule (VCAM), and the deleted in colorectal cancer (DCC) receptor. We also analyze the ezrin-meditated regulation of critical pathways associated with asthma, such as the RhoA, Rho-associated protein kinase (ROCK), and protein kinase A (cAMP/PKA) pathways...
July 13, 2017: Reviews of Physiology, Biochemistry and Pharmacology
https://www.readbyqxmd.com/read/28698359/egfr-down-regulation-after-anti-egfr-therapy-predicts-the-anti-tumor-effect-in-colorectal-cancer
#8
Yasuyuki Okada, Tetsuo Kimura, Tadahiko Nakagawa, Koichi Okamoto, Akira Fukuya, Takahiro Goji, Shota Fujimoto, Masahiro Sogabe, Hiroshi Miyamoto, Naoki Muguruma, Yasushi Tsuji, Toshiya Okahisa, Tetsuji Takayama
Anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) is reported to induce EGFR internalization in colorectal cancer (CRC) cells. However, the biological relevance of EGFR internalization with anti-EGFR mAb is unknown. Therefore, the relevance of EGFR downregulation with anti-EGFR mAb to anti-tumor activity in CRC cells was investigated. Quantification of EGFR on the cell surface before cetuximab treatment was assessed by flow cytometry, and its growth-inhibitory effects were measured by trypan blue-exclusion, in 10 RAS, BRAF wild-type CRC cell lines, but there was no significant correlation between EGFR number and its growth-inhibitory effect...
July 11, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28695301/optimal-use-of-anti-egfr-monoclonal-antibodies-for-patients-with-advanced-colorectal-cancer-a-meta-analysis
#9
REVIEW
E J van Helden, C W Menke-van der Houven van Oordt, M W Heymans, J C F Ket, R van den Oord, H M W Verheul
This meta-analysis was performed to determine the optimal use of anti-EGFR mAb in the treatment of metastasized colorectal cancer (mCRC). Seventeen randomized clinical trials were included, all evaluating the added value of anti-EGFR mAb to standard treatment line in patients with KRAS wild-type mCRC. Hazard and odds ratios were pooled using a random effect model, weighted according to cohort size. Pooled data of six first- and two second-line studies demonstrated a significantly improved ORR (OR 1.62, CI 1...
July 10, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28692881/detection-of-kras-exon-2-mutations-in-circulating-tumor-cells-isolated-by-the-iset-system-from-patients-with-ras-wild-type-metastatic-colorectal-cancer
#10
Alexios Matikas, Alexandra Voutsina, Eleni Lagoudaki, Dora Hatzidaki, Maria Trypaki, Giannis Stoupis, Maria Tzardi, Dimitrios Mavroudis, Vasilios Georgoulias
INTRODUCTION: The presence of KRAS mutations in patients with metastatic colorectal cancer (mCRC) predicts poor response to agents targeting the EGFR. Even in patients with RAS wild type (WT) tumors, resistance eventually develops due to multiple mechanisms, including the expansion of previously undetected KRAS mutated clones. In this feasibility study, we aimed to detect KRAS exon 2 mutations in serial samples of circulating tumor cells (CTCs) of RAS WT patients with mCRC captured by the Isolation by Size of Epithelial Tumor cells (ISET) system...
July 7, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28688743/-detection-of-ras-genes-mutation-using-the-cobas-%C3%A2-method-in-a-private-laboratory-of-pathology-medical-and-economical-study-in-comparison-to-a-public-platform-of-molecular-biology-of-cancer
#11
Anne-Flore Albertini, Delphine Raoux, Frédéric Neumann, Stéphane Rossat, Farid Tabet, Florence Pedeutour, Valérie Duranton-Tanneur, Valérie Kubiniek, Olivier Vire, Nicolas Weinbreck
In France, determination of the mutation status of RAS genes for predictive response to anti-EGFR targeted treatments is carried out by public platforms of molecular biology of cancer created by the French National Cancer Institute. This study aims to demonstrate the feasibility of these analyses by a private pathology laboratory (MEDIPATH) as per the requirements of accreditation. We retrospectively studied the mutation status of KRAS and NRAS genes in 163 cases of colorectal metastatic cancer using the Cobas(®) technique...
July 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28687332/systemic-analysis-of-different-colorectal-cancer-cell-lines-and-tcga-datasets-identified-igf-1r-egfr-ppar-caspase-axis-as-important-indicator-for-radiotherapy-sensitivity
#12
Lin Chen, Zhe Zhu, Wei Gao, Qixin Jiang, Jiangming Yu, Chuangang Fu
Insulin-like growth factor 1 receptor (IGF-1R) is proved to contribute the development of many types of cancers. But, little is known about its roles in radio-resistance of colorectal cancer (CRC). Here, we demonstrated that low IGF-1R expression value was associated with the better radiotherapy sensitivity of CRC. Besides, through Quantitative Real-time PCR (qRT-PCR), the elevated expression value of epidermal growth factor receptor (EGFR) was observed in CRC cell lines (HT29, RKO) with high radio-sensitivity compared with those with low sensitivity (SW480, LOVO)...
July 4, 2017: Gene
https://www.readbyqxmd.com/read/28685592/investigation-of-correlation-between-mutational-status-in-key-egfr-signaling-genes-and-prognosis-of-stage-ii-colorectal-cancer
#13
Li Li, Bei-Bei Ni, Qing-Hua Zhong, Yan-Hui Liu, Ming-Hui Zhang, Ke-Ping Zhang, Dai-Ci Chen, Lei Wang
AIM: To investigate the relationship between mutations of key genes in the EGFR signaling pathway and the prognosis of stage II colorectal cancer patients without chemotherapy. MATERIALS & METHODS: The incidence of KRAS, NRAS, BRAF, PIK3CA mutations and deficient DNA mismatch repair were assessed in 160 stage II colorectal cancer patients who had been treated by radical operation without adjuvant chemotherapy. RESULTS: Mutations in KRAS, BRAF or PIK3CA were associated with poor prognosis, while the deficient DNA mismatch repair status was not associated with the prognosis...
July 7, 2017: Future Oncology
https://www.readbyqxmd.com/read/28685087/heterogeneity-in-the-colorectal-primary-tumor-and-the-synchronous-resected-liver-metastases-prior-to-and-after-treatment-with-an-anti-egfr-monoclonal-antibody
#14
Daniela Adua, Francesca Di Fabio, Giorgio Ercolani, Michelangelo Fiorentino, Elisa Gruppioni, Annalisa Altimari, Fabiola Lorena Rojas Limpe, Nicola Normanno, Antonio Daniele Pinna, Carmine Pinto
Molecular heterogeneity between primary tumors (PTs) and synchronous resected liver metastasis in colorectal cancer (CRC) has potential relevance in treatment strategies. Next-generation sequencing (NGS) may be able to increase the chances of identifying multiple molecular driver alterations, calling for therapy. The aim of the present study was to evaluate mutations in PT and synchronous resected liver metastases for patients with Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) exon 2 wild-type metastatic (m)CRC who underwent chemotherapy (CT) featuring an anti-epidermal growth factor receptor (EGFR) monoclonal antibody...
July 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28682222/the-clinical-effectiveness-and-cost-effectiveness-of-cetuximab-review-of-technology-appraisal-no-176-and-panitumumab-partial-review-of-technology-appraisal-no-240-for-previously-untreated-metastatic-colorectal-cancer-a-systematic-review-and-economic-evaluation
#15
Nicola Huxley, Louise Crathorne, Jo Varley-Campbell, Irina Tikhonova, Tristan Snowsill, Simon Briscoe, Jaime Peters, Mary Bond, Mark Napier, Martin Hoyle
BACKGROUND: Colorectal cancer is the fourth most commonly diagnosed cancer in the UK after breast, lung and prostate cancer. People with metastatic disease who are sufficiently fit are usually treated with active chemotherapy as first- or second-line therapy. Targeted agents are available, including the antiepidermal growth factor receptor (EGFR) agents cetuximab (Erbitux(®), Merck Serono UK Ltd, Feltham, UK) and panitumumab (Vecitibix(®), Amgen UK Ltd, Cambridge, UK). OBJECTIVE: To investigate the clinical effectiveness and cost-effectiveness of panitumumab in combination with chemotherapy and cetuximab in combination with chemotherapy for rat sarcoma (RAS) wild-type (WT) patients for the first-line treatment of metastatic colorectal cancer...
June 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28674212/therapeutic-efficacy-of-sym004-a-mixture-of-two-anti-egfr-antibodies-in-human-colorectal-cancer-with-acquired-resistance-to-cetuximab-and-met-activation
#16
Stefania Napolitano, Giulia Martini, Erika Martinelli, Valentina Belli, Alessia Parascandolo, Mikko O Laukkanen, Vincenzo Sforza, Floriana Morgillo, Davide Ciardiello, Fortunato Ciardiello, Teresa Troiani
PURPOSE: Cetuximab and panitumumab have an effective therapeutic response in a subset of RAS Wild-Type (WT) metastatic colorectal cancers (mCRCs). Despite molecular-driven selection, all patients do not respond to epidermal growth factor receptor (EGFR) inhibitors and the onset of secondary resistance limits their clinical benefit. EXPERIMENTAL DESIGN: We tested, in vitro and in vivo, the effect of SYM004, a 1:1 mixture of two recombinant human-mouse chimeric monoclonal antibodies (mAbs) directed against non-overlapping epitopes of the EGFR, on CRC models with acquired resistance to cetuximab...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28670764/microrna-375-regulates-proliferation-and-migration-of-colon-cancer-cells-by-suppressing-the-ctgf-egfr-signaling-pathway
#17
Khondoker Jahengir Alam, Ji-Su Mo, Seol-Hee Han, Won-Cheol Park, Hun-Soo Kim, Ki-Jung Yun, Soo-Cheon Chae
MicroRNA 375 (MIR375) is significantly down regulated in human colorectal cancer (CRC) tissues; we have previously identified MIR375 as a colon cancer associated microRNA (miRNA). We identified putative MIR375 target genes by comparing the mRNA microarray analysis data of MIR375-overexpressing cells with the candidate MIR375 target genes predicted by public bioinformatic tools. We investigated that the connective tissue growth factor (CTGF) is a direct target gene of MIR375. Expression of CTGF, a ligand of epidermal growth factor receptor (EGFR), was markedly enhanced in human CRC tissues in comparison with the corresponding normal colon tissues...
July 3, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28670133/skin-toxicity-evaluation-in-patients-treated-with-cetuximab-for-metastatic-colorectal-cancer-a-new-tool-for-more-accurate-comprehension-of-quality-of-life-impacts
#18
Michele De Tursi, Marinella Zilli, Consiglia Carella, Matteo Auriemma, Maria Nadia Lisco, Marta Di Nicola, Giuseppe Di Martino, Clara Natoli, Paolo Amerio
OBJECTIVES: The effectiveness of evaluation of the severity of epidermal growth-factor receptor inhibitor (EGFRI)-associated dermatological toxicities remains a topic of debate. This study was designed to assess the correlation between quality of life (QoL) and severity of dermatological toxicity, evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) and our novel scale, the Eruption Scoring System (ESS), in metastatic colorectal cancer (CRC) patients treated with first-line chemotherapy combined with cetuximab...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28665451/discordance-in-ras-mutations-between-primary-colon-tumor-and-metastases-a-real-event-or-a-matter-of-methodology
#19
Alfonso De Stefano, Mario Rosanova, Umberto Malapelle, Maurizio Martini, Stefano De Falco, Laura Attademo, Giovanni Fiore, Tonia Cenci, Claudio Bellevicine, Sabino De Placido, Giancarlo Troncone, Chiara Carlomagno
BACKGROUND: Analysis of K- and N-RAS mutations is mandatory before planning treatment of metastatic colorectal cancer, because only RAS wild-type (WT) patients can benefit from treatment with anti-EGFR monoclonal antibodies (cetuximab and panitumumab). CASE REPORT: Here we report the case of a 69-year-old male patient affected by metastatic sigmoid cancer. He underwent left hemicolectomy, and histology diagnosed a well-differentiated, pT4, node-positive adenocarcinoma; KRAS analysis performed with direct sequencing identified a mutation in exon 2 of the KRAS gene (GGT->GTT)...
June 20, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28654140/epidermal-growth-factor-receptor-egfr-inhibitors-for-metastatic-colorectal-cancer
#20
REVIEW
David Lok Hang Chan, Eva Segelov, Rachel Sh Wong, Annabel Smith, Rebecca A Herbertson, Bob T Li, Niall Tebbutt, Timothy Price, Nick Pavlakis
BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors prevent cell growth and have shown benefit in the treatment of metastatic colorectal cancer, whether used as single agents or in combination with chemotherapy. Clear benefit has been shown in trials of EGFR monoclonal antibodies (EGFR MAb) but not EGFR tyrosine kinase inhibitors (EGFR TKI). However, there is ongoing debate as to which patient populations gain maximum benefit from EGFR inhibition and where they should be used in the metastatic colorectal cancer treatment paradigm to maximise efficacy and minimise toxicity...
June 27, 2017: Cochrane Database of Systematic Reviews
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