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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
#1
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/28708307/evaluation-of-short-term-effectiveness-of-eight-targeted-agents-combined-with-chemotherapy-for-treating-esophageal-gastric-junction-adenocarcinoma-a-network-meta-analysis
#2
Yong-Ming He, Chen Yu, Wei-Bing Li, Zhi-Peng Li, Nan Xu
This study aimed to evaluate the short-term effectiveness of eight targeted agents (ramucirumab, bevacizumab, rilotumumab, panitumumab, cetuximab, trebananib, trastuzumab, matuzumab) plus chemotherapy in esophageal-gastric junction adenocarcinoma (EGJA) by a network meta-analysis (NMA). PubMed, Embase, and Cochrane Library databases were systematically retrieved for randomized clinical trials (RCTs) concerning targeted agents plus chemotherapy in the treatment of EGJA. This NMA combined both direct and indirect evidence to evaluate odds ratio (OR) and to draw the surface under the cumulative ranking curve (SUCRA)...
July 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28708103/pharmacogenomics-of-targeted-agents-for-personalization-of-colorectal-cancer-treatment
#3
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/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
#4
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
#5
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/28665451/discordance-in-ras-mutations-between-primary-colon-tumor-and-metastases-a-real-event-or-a-matter-of-methodology
#6
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/28633089/first-line-panitumumab-plus-folfox4-or-folfiri-in-colorectal-cancer-with-multiple-or-unresectable-liver-metastases-a-randomised-phase-ii-trial-planet-ttd
#7
Alfredo Carrato, Albert Abad, Bartomeu Massuti, Cristina Grávalos, Pilar Escudero, Federico Longo-Muñoz, José-Luis Manzano, Auxiliadora Gómez, María José Safont, Javier Gallego, Beatriz García-Paredes, Carles Pericay, Rosario Dueñas, Fernando Rivera, Ferrán Losa, Manuel Valladares-Ayerbes, Encarnación González, Enrique Aranda
BACKGROUND: In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue (KRAS) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]. However no trial has directly compared these combinations. METHODS: Multicentre, open-label study in untreated patients ≥ 18 years with (WT)-KRAS mCRC and multiple or unresectable liver-limited disease (LLD) randomised to either Pmab-FOLFOX4 or Pmab-FOLFIRI...
August 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28629896/randomized-phase-ii-study-of-preoperative-chemoradiotherapy-panitumumab-followed-by-consolidation-chemotherapy-in-potentially-operable-locally-advanced-stage-iiia-n2-non-small-cell-lung-cancer-nrg-oncology-rtog-0839
#8
Martin J Edelman, Chen Hu, Quynh-Thu Le, Jessica S Donington, Warren D D'Souza, Adam P Dicker, Billy W Loo, Elizabeth M Gore, Gregory M M Videtic, Nathaniel R Evans, Joseph W Leach, Maximilian Diehn, Steven J Feigenberg, Yuhchyau Chen, Rebecca Paulus, Jeffrey D Bradley
INTRODUCTION: Multimodality therapy has curative potential in locally advanced non-small cell lung cancer (LASCLC). Mediastinal nodal sterilization (MNS) after induction chemoradiotherapy (CRT) can serve as an intermediate marker for efficacy. NRG Oncology RTOG 0229 demonstrated the feasibility and efficacy of combining full dose radiation (61.2Gy) with chemotherapy followed by resection and chemotherapy. Based upon that experience and evidence that epidermal growth factor receptor (EGFR) antibodies are radiosensitizing, we explored adding panitumumab to CRT followed by resection and consolidation chemotherapy in LANSCLC with a primary endpoint of MNS...
June 16, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28622036/molecular-targeted-drugs-and-treatment-of-colorectal-cancer-recent-progress-and-future-perspectives
#9
Fang Geng, Zheng Wang, Hang Yin, Junxian Yu, Bangwei Cao
Nowadays, colorectal cancer is the fourth most common type of tumor all over the world. When diagnosed, ∼50%-60% of tumors have metastasized, thus resulting in a grim prognosis. Chemotherapy is regarded as standard treatment for patients with colorectal cancer, however, limitations of chemotherapy cannot be ignored, such as low selectivity, insufficient concentrations in tumor tissues, and systemic toxicity. Recently, six targeted drugs have been approved by the U.S. Food and Drug Administration (FDA) for treatment of metastatic colorectal cancer (mCRC), including bevacizumab, aflibercept, regorafenib, cetuximab, and panitumumab...
June 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28619755/epidermal-growth-factor-receptor-egfr-targeted-photoimmunotherapy-pit-for-the-treatment-of-egfr-expressing-bladder-cancer
#10
Reema Railkar, L Spencer Krane, Q Quentin Li, Thomas Sanford, Mohammad Rashid Siddiqui, Diana Haines, Srinivas Vourganti, Sam J Brancato, Peter L Choyke, Hisataka Kobayashi, Piyush K Agarwal
The use of light as a means of therapy for bladder cancer (BC) has a long history but has been hampered by a lack of tumor specificity and therefore, damage to the normal bladder mucosa. Here, we describe a targeted form of photo-therapy called photoimmunotherapy (PIT) which targets EGFR-expressing BC. Anti-EGFR antibody panitumumab (pan) was labeled with the photo-absorber (PA), IRDye 700Dx (IR700), to create a pan IR700 antibody-PA conjugate which is activated by near-infrared radiation (NIR). BC tissue microarray (TMA) and BC cell lines were analyzed for expression of EGFR...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28602170/treatment-options-for-metastatic-colorectal-cancer-in-patients-with-liver-dysfunction-due-to-malignancy
#11
REVIEW
L Faugeras, A Dili, A Druez, B Krug, C Decoster, L D'Hondt
BACKGROUND: The survival of colorectal cancer patients is frequently determined by the extent of metastatic invasion to the liver; in cases of major involvement, therapeutic strategies are limited because the liver is necessary for drug metabolism. MATERIAL AND METHODS: We have reviewed articles about the pharmacokinetic profiles of each drug used in colorectal cancer patients with hepatic dysfunction to determine which of these treatments are most feasible. RESULTS: Some drugs appear to be feasible options for patients with hepatic insufficiency...
July 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28592616/multicenter-phase-ii-study-of-panitumumab-in-platinum-pretreated-advanced-head-and-neck-squamous-cell-cancer
#12
Marco Siano, Francesca Molinari, Vittoria Martin, Nicolas Mach, Martin Früh, Stefania Freguia, Irene Corradino, Michele Ghielmini, Milo Frattini, Vittoria Espeli
LESSONS LEARNED: Panitumumab shows activity in terms of disease control rate and preventing disease progression but not for tumor shrinkage in head and neck squamous cell cancer for second-line treatment. Epidermal growth factor receptor (EGFR) copy number gain, a property of tumor cells that theoretically could identify patients more likely to experience disease response, was common among patients having disease control.Our trial, given the lower toxicity with an every-2-week schedule, provides guidance for future trials, for example, in combinations of immune therapies and anti-EGFR-antibodies...
July 2017: Oncologist
https://www.readbyqxmd.com/read/28577439/targeted-%C3%AE-particle-radiation-therapy-of-her1-positive-disseminated-intraperitoneal-disease-an-investigation-of-the-human-anti-egfr-monoclonal-antibody-panitumumab
#13
Diane E Milenic, Kwamena E Baidoo, Young-Seung Kim, Rachel Barkley, Martin W Brechbiel
Identifying molecular targets and an appropriate targeting vehicle, i.e., monoclonal antibodies (mAb) and their various forms, for radioimmunotherapy (RIT) remains an active area of research. Panitumumab, a fully human and less immunogenic mAb that binds to the epidermal growth factor receptor (Erb1; HER1), was evaluated for targeted α-particle radiation therapy using (212)Pb, an in vivo α generator. A single dose of (212)Pb-panitumumab administered to athymic mice bearing LS-174T intraperitoneal (i.p.) tumor xenografts was found to have greater therapeutic efficacy when directly compared with (212)Pb-trastuzumab, which binds to HER2...
May 31, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28576857/braf-mutations-as-predictive-biomarker-for-response-to-anti-egfr-monoclonal-antibodies
#14
REVIEW
Emilie M J van Brummelen, Anthonius de Boer, Jos H Beijnen, Jan H M Schellens
Recently, the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) recommended that patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer could be treated with anti-EGFR monoclonal antibodies (mAbs) cetuximab and panitumumab only in absence of Rat-Sarcoma (RAS) mutations. In addition to the previously established biomarker Kirsten rat sarcoma viral oncogene homolog (KRAS) exon 2, cumulative evidence also shows that patients whose tumors harbor KRAS exons 3 or 4 and neuroblastoma rat-sarcoma viral oncogene homolog (NRAS) exons 2, 3, and 4 mutations are found unlikely to benefit from anti-EGFR treatment...
July 2017: Oncologist
https://www.readbyqxmd.com/read/28531891/dual-inhibition-of-egfr-and-vegf-in-heavily-pretreated-patients-with-metastatic-colorectal-cancer
#15
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/28507280/molecular-dissection-of-effector-mechanisms-of-ras-mediated-resistance-to-anti-egfr-antibody-therapy
#16
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...
July 11, 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
#17
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/28456787/predictive-blood-plasma-biomarkers-for-egfr-inhibitor-induced-skin-rash
#18
Vivien Hichert, Catharina Scholl, Michael Steffens, Tanusree Paul, Christian Schumann, Stefan Rüdiger, Stefan Boeck, Volker Heinemann, Volker Kächele, Thomas Seufferlein, Julia Stingl
Epidermal growth factor receptor overexpression in human cancer can be effectively targeted by drugs acting as specific inhibitors of the receptor, like erlotinib, gefitinib, cetuximab and panitumumab. A common adverse effect is a typical papulopustular acneiform rash, whose occurrence and severity are positively correlated with overall survival in several cancer types. We studied molecules involved in epidermal growth factor receptor signaling which are quantifiable in plasma, with the aim of identifying biomarkers for the severity of rash...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28449055/primary-tumor-sidedness-has-an-impact-on-prognosis-and-treatment-outcome-in-metastatic-colorectal-cancer-results-from-two-randomized-first-line-panitumumab-studies
#19
N Boeckx, R Koukakis, K Op de Beeck, C Rolfo, G Van Camp, S Siena, J Tabernero, J-Y Douillard, T André, M Peeters
Background: : Previous studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors. Material and methods: Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients...
April 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28439399/posterior-reversible-encephalopathy-syndrome-with-colitis-in-a-patient-treated-with-panitumumab
#20
Céline Blaye, Xavier Buy, Marine Gross-Goupil, Didier Vincent, Claire Jamet, Paul Sargos, Stéphane Culine, Guilhem Roubaud
No abstract text is available yet for this article.
April 2017: Therapeutic Advances in Drug Safety
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