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Cetuximab

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https://www.readbyqxmd.com/read/29792310/bet-inhibition-overcomes-receptor-tyrosine-kinase-mediated-cetuximab-resistance-in-hnscc
#1
Brandon Leonard, Toni M Brand, Rachel A O'Keefe, Eliot Lee, Yan Zang, Jacquelyn D Kemmer, Hua Li, Jennifer R Grandis, Neil E Bhola
Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK) including HER3, MET, and AXL. In an effort to overcome cetuximab resistance and circumvent toxicities associated with the administration of multiple RTK inhibitors, we sought to identify a common molecular target that regulates expression of multiple RTK...
May 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29792227/integrated-time-course-omics-analysis-distinguishes-immediate-therapeutic-response-from-acquired-resistance
#2
Genevieve Stein-O'Brien, Luciane T Kagohara, Sijia Li, Manjusha Thakar, Ruchira Ranaweera, Hiroyuki Ozawa, Haixia Cheng, Michael Considine, Sandra Schmitz, Alexander V Favorov, Ludmila V Danilova, Joseph A Califano, Evgeny Izumchenko, Daria A Gaykalova, Christine H Chung, Elana J Fertig
BACKGROUND: Targeted therapies specifically act by blocking the activity of proteins that are encoded by genes critical for tumorigenesis. However, most cancers acquire resistance and long-term disease remission is rarely observed. Understanding the time course of molecular changes responsible for the development of acquired resistance could enable optimization of patients' treatment options. Clinically, acquired therapeutic resistance can only be studied at a single time point in resistant tumors...
May 23, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29790314/superselective-intraarterial-cerebral-infusion-of-cetuximab-with-blood-brain-barrier-disruption-combined-with-stupp-protocol-for-newly-diagnosed-glioblastoma
#3
Kay O Kulason, Julia R Schneider, Shamik Chakraborty, Christopher G Filippi, Bidyut Pramanik, Tamika Wong, Sherese Fralin, Karissa Tan, Ashley Ray, Rachel A Alter, Rafael Ortiz, Alexis Demopoulos, David J Langer, John A Boockvar
We describe the first case of a novel treatment for a newly diagnosed glioblastoma (GBM) using superselective intraarterial cerebral infusion (SIACI) of cetuximab after osmotic disruption of the blood-brain barrier (BBB) with mannitol. A 51year-old female underwent craniotomy for removal of a right frontal GBM. Pathology confirmed EGFR amplification, and she underwent three treatments of SIACI of cetuximab to the tumor site. The first treatment was given within a week of starting standard of care chemoradiation (Stupp protocol), which is a combination of radiation treatment (2 Gy per/ day x 30 days, total of 60 Gy) and oral temozolomide (75 mg/m2 )...
May 2018: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/29784451/randomized-trial-comparing-two-methods-of-re-irradiation-after-salvage-surgery-in-head-and-neck-squamous-cell-carcinoma-once-daily-split-course-radiotherapy-with-concomitant-chemotherapy-or-twice-daily-radiotherapy-with-cetuximab
#4
Yungan Tao, Laura Faivre, Anne Laprie, Pierre Boisselier, Christophe Ferron, Guy Michel Jung, Séverine Racadot, Bernard Gery, Caroline Even, Ingrid Breuskin, Jean Bourhis, François Janot
BACKGROUND: A previous randomized trial in recurrent Head and Neck squamous-cell carcinoma (HNSCC) has shown re-irradiation combined with chemotherapy after salvage surgery significantly improved disease-free survival (DFS). The objective of this randomized trial was to compare two methods of re-irradiation in terms of toxicity and survival. PATIENTS AND METHODS: Patients with recurrence/second primary in previously irradiated area were randomly allocated to receive either 60 Gy over 11 weeks with concomitant 5FU - hydroxyurea (VP-arm), or 60 Gy (1...
May 18, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29777999/targeted-delivery-of-cd44s-sirna-by-scfv-overcomes-de-novo-resistance-to-cetuximab-in-triple-negative-breast-cancer
#5
Wenyan Fu, Hefen Sun, Yang Zhao, Mengting Chen, Lipeng Yang, Xueli Yang, Wei Jin
The overexpression of EGFR often occurs in TNBC, and the anti-EGFR receptor antibody cetuximab is used widely to treat metastatic cancer in the clinic. However, EGFR-targeted therapies have been developed for TNBC without clinical success. In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP...
May 16, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29777587/epidermal-growth-factor-receptor-egfr-density-may-not-be-the-only-determinant-for-the-efficacy-of-egfr-targeted-photoimmunotherapy-in-human-head-and-neck-cancer-cell-lines
#6
Wei Peng, Henriette S de Bruijn, Eric Farrell, Mouldy Sioud, Vida Mashayekhi, Sabrina Oliveira, Go M van Dam, Jan L N Roodenburg, Max J H Witjes, Dominic J Robinson
OBJECTIVE: The aim of this study was to investigate the effects of targeted photoimmunotherapy (PIT) in vitro on cell lines with various expression levels of epidermal growth factor receptor (EGFR) using an anti-EGFR targeted conjugate composed of Cetuximab and IR700DX, phthalocyanine dye. MATERIALS AND METHODS: Relative EGFR density and cell binding assay was conducted in three human head & neck cancer cell lines (scc-U2, scc-U8, and OSC19) and one reference cell line A431...
May 19, 2018: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/29777377/radiolabeled-f-ab-2-cetuximab-for-theranostic-purposes-in-colorectal-and-skin-tumor-bearing-mice-models
#7
P-S Bellaye, M Moreau, O Raguin, A Oudot, C Bernhard, J-M Vrigneaud, L Dumont, D Vandroux, F Denat, A Cochet, F Brunotte, B Collin
PURPOSE: This study aimed to investigate theranostic strategies in colorectal and skin cancer based on fragments of cetuximab, an anti-EGFR mAb, labeled with radionuclide with imaging and therapeutic properties, 111 In and 177 Lu, respectively. METHODS: We designed F(ab')2 -fragments of cetuximab radiolabeled with 111 In and 177 Lu. 111 In-F(ab')2 -cetuximab tumor targeting and biodistribution were evaluated by SPECT in BalbC nude mice bearing primary colorectal tumors...
May 17, 2018: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29775397/receptor-tyrosine-kinase-signaling-in-cancer-radiotherapy-and-its-targeting-for-tumor-radiosensitization
#8
Poushali Bhattacharya, Neena G Shetake, Badri N Pandey, Amit Kumar
PURPOSE: One of the most important implications of 'Radiation Biology' research is to improve cancer radiotherapy with minimum side effects. In this regard, combination of chemotherapy with radiation has significantly improved tumor control as well as overall survival in a variety of cancers. However, this has been achieved at the cost of significant normal tissue toxicity, due to the lack of specificity of chemotherapy. Membrane-localized receptor tyrosine kinases (RTKs) have been found to play a driving role in various hallmarks of cancer...
May 18, 2018: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29774120/carboplatin-in-combination-with-weekly-paclitaxel-as-first-line-therapy-in-patients-with-recurrent-metastatic-head-and-neck-squamous-cell-carcinoma-unfit-to-extreme-schedule
#9
Adeline Pêtre, Cécile Dalban, Andy Karabajakian, Eve-Marie Neidhardt, Pierre Eric Roux, Marc Poupart, Sophie Deneuve, Philippe Zrounba, Jérome Fayette
The standard first-line treatment in recurrent/metastatic head and neck squamous cell carcinoma combines Cisplatin, 5 Fluorouracil and Cetuximab, but many patients aren't eligible. We retrospectively evaluated the efficacy and the tolerability of Carboplatin and Paclitaxel in this indication, mostly in patients unfit to Cisplatin. Paclitaxel (80mg/m2) was administered at day 1, 8 and 15 and Carboplatin area under the curve 5 at day 1, repeated every 28 days, for 6 cycles. Carboplatin could be administered at area under the curve 2 at day 1, 8 and 15...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29769385/phase-ii-study-of-irinotecan-plus-panitumumab-as-second-line-therapy-for-patients-with-advanced-esophageal-adenocarcinoma
#10
Harry Yoon, Anita Choudhary, Ramla Kosozi, Gurvinder Singh Bali, Ali Zaidi, Ajlan Atasoy, Arlene A Forastiere, Michael K Gibson
LESSON LEARNED: Panitumumab plus irinotecan is not active for the treatment of esophageal adenocarcinoma. BACKGROUND: Esophageal adenocarcinoma (EAC) is a lethal cancer with increasing incidence. Panitumumab (Pa) is a fully humanized IgG2 monoclonal antibody against human EGFR. Cetuximab (Cx) combined with irinotecan (Ir) is active for second-line treatment of colorectal cancer. This phase II study was designed to evaluate Pa plus Ir as second-line therapy for advanced EAC...
May 16, 2018: Oncologist
https://www.readbyqxmd.com/read/29765773/optimising-the-use-of-cetuximab-in-the-continuum-of-care-for-patients-with-metastatic-colorectal-cancer
#11
REVIEW
Richard M Goldberg, Clara Montagut, Zev A Wainberg, Philippe Ronga, François Audhuy, Julien Taieb, Sebastian Stintzing, Salvatore Siena, Daniele Santini
The anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in combination with chemotherapy is a standard of care in the first-line treatment of RAS wild-type (wt) metastatic colorectal cancer (mCRC) and has demonstrated efficacy in later lines. Progressive disease (PD) occurs when tumours develop resistance to a therapy, although controversy remains about whether PD on a combination of chemotherapy and targeted agents implies resistance to both components. Here, we propose that some patients may gain additional clinical benefit from the reuse of cetuximab after having PD on regimens including cetuximab in an earlier treatment line...
2018: ESMO Open
https://www.readbyqxmd.com/read/29760803/effectiveness-of-cetuximab-in-combination-with-concurrent-chemoradiotherapy-in-locoregionally-advanced-nasopharyngeal-carcinoma-a-1-2-propensity-score-matched-analysis
#12
Li-Rong Wu, Huan-Feng Zhu, Jianhua Xu, Xue-Song Jiang, Li Yin, Ning Jiang, Dan Zong, Fei-Jiang Wang, Sheng-Fu Huang, Xiu-Hua Bian, Jian-Feng Wu, Dan Song, Wen-Jie Guo, Ju-Ying Liu, Xia He
Background : This study aimed to compare concurrent chemoradiotherapy (CCRT) plus cetuximab (C) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma(NPC). Methods : A total of 682 locoregionally advanced NPC patients who had undergone chemoradiotherapy with or without cetuximab were included. Propensity score-matching method was used to match patients. Progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between the two treatment arms...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29756421/survey-of-cutaneous-adverse-reactions-to-targeted-cancer-therapies-value-of-dermatological-advice
#13
Giovanni Damiani, Ausilia Manganoni, Simone Cazzaniga, Luigi Naldi
BACKGROUND: Target-therapy offers a better efficacy for several cancers, with less toxic adverse effects, if compared with traditional chemotherapy. However cutaneous complications are increased in number and complexity. The severity of these reactions positively correlates with efficacy, and the management of these reactions is challenging. METHODS: This was a multicenter cross-sectional study on a consecutive series of adult patients with incident cutaneous reactions linked to targeted cancer therapies observed in five referral centers for cancer treatment in the province of Bergamo and Brescia in northern Italy...
May 11, 2018: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/29755619/molecularly-targeted-therapy-for-the-oral-cancer-stem-cells
#14
REVIEW
Yuichi Ohnishi, Hiroki Yasui, Masami Nozaki, Masahiro Nakajima
Human cancer tissues are heterogeneous in nature and become differentiated during expansion of cancer stem cells (CSCs). CSCs initiate tumorigenesis, and are involved in tumor recurrence and metastasis. Furthermore, data show that CSCs are highly resistant to anticancer drugs. Cetuximab, a specific anti-epidermal growth factor receptor (EGFR) monoclonal antibody, is used in cancer treatment. Although development of resistance to cetuximab is well recognized, the underlying mechanisms remain unclear. Lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR)/ErbB2, has antiproliferative effects and is used to treat patients with ErbB2-positive metastatic breast cancer...
May 2018: Japanese Dental Science Review
https://www.readbyqxmd.com/read/29755130/restoring-puma-induction-overcomes-kras-mediated-resistance-to-anti-egfr-antibodies-in-colorectal-cancer
#15
Kyle Knickelbein, Jingshan Tong, Dongshi Chen, Yi-Jun Wang, Sandra Misale, Alberto Bardelli, Jian Yu, Lin Zhang
Intrinsic and acquired resistance to anti-EGFR antibody therapy, frequently mediated by a mutant or amplified KRAS oncogene, is a significant challenge in the treatment of colorectal cancer (CRC). However, the mechanism of KRAS-mediated therapeutic resistance is not well understood. In this study, we demonstrate that clinically used anti-EGFR antibodies, including cetuximab and panitumumab, induce killing of sensitive CRC cells through p73-dependent transcriptional activation of the pro-apoptotic Bcl-2 family protein PUMA...
May 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29755114/az304-a-novel-dual-braf-inhibitor-exerts-anti-tumour-effects-in-colorectal-cancer-independently-of-braf-genetic-status
#16
Rui Ma, Ling Xu, Xiujuan Qu, Xiaofang Che, Ye Zhang, Yibo Fan, Ce Li, Tianshu Guo, Kezuo Hou, Xuejun Hu, Lisa Drew, Minhui Shen, Tony Cheung, Yunpeng Liu
BACKGROUND: BRAF mutation is associated with poor clinical outcome of patients with malignant tumours, and mediates resistance to chemotherapy and targeted therapy. This study aimed to determine whether V600E mutant and wild type BRAF colorectal cancers exhibit distinct sensitivities to the dual BRAF inhibitor AZ304. METHODS: Kinase activity was assessed by the AlphaScreen assay. Then, MTT assay, EdU assay, colony-formation assay and Western blot were performed to evaluate the anti-tumour effects of AZ304 in vitro...
May 14, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29747544/deep-hyperthermia-with-the-hypercollar-system-combined-with-irradiation-for-advanced-head-and-neck-carcinoma-a-feasibility-study
#17
G M Verduijn, E M de Wee, Z Rijnen, P Togni, J A U Hardillo, I Ten Hove, M Franckena, G C van Rhoon, M M Paulides
PURPOSE: Radiotherapy (RT) treatment of locally-advanced and recurrent head and neck carcinoma (HNC) results in disappointing outcomes. Combination of RT with cisplatin or cetuximab improves survival but the increased toxicity and patient's comorbidity warrant the need for a less-toxic radiosensitizer. Stimulated by several randomized studies demonstrating the radio-sensitizing effect of hyperthermia, we developed the HYPERcollar. Here, we report early experience and toxicity in patients with advanced HNC...
May 11, 2018: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/29745068/topics-related-to-neoadjuvant-chemotherapy-for-resectable-liver-metastases-from-colorectal-cancer
#18
Shanbao Ke, Shufang Zhan, Hongbo Zhu, Danfang Yan
Metastases to the liver from colorectal cancer (CRC) are common, and only a minority of patients are candidates for upfront surgery at the initial diagnosis. Carefully selected patients can achieve long-term survival from surgery with curative intent. Unfortunately, the risk of recurrence remains substantial after liver resection. In order to reduce the risk of relapse and improve the outcomes, the role of neoadjuvant chemotherapy has been assessed for resectable colorectal liver metastases (CRLM) with an improvement in progression-free survival (PFS)...
March 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29740494/addition-of-bevacizumab-to-systemic-therapy-for-locally-advanced-and-metastatic-nasopharyngeal-carcinoma
#19
Hui-Jie Zhang, Gao-Le Yuan, Qi-Lian Liang, Xiao-Xia Peng, Shao-Ang Cheng, Liang Jiang
Radiotherapy is a vital treatment option for patients with nasopharyngeal carcinoma (NPC). Concurrent cisplatin-based radiochemotherapy with or without adjuvant chemotherapy had acquired good clinical effects with good local control rates. However, a number of patients present with metastasis following systemic regimens or initial diagnosis of locally advanced NPC, which cause difficulty for subsequent therapy. Therefore, there is an urgent requirement to discover novel targeted therapies. The present report describes one case of a patient with NPC and multiple metastases...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29734190/severe-pain-due-to-paraspinal-abscess-formation-in-two-patients-with-squamous-cell-carcinoma-of-the-head-and-neck-after-multimodal-treatment-including-cetuximab
#20
Christina Gerlach, Ina Pretzell, Elisabeth Lieberknecht, Stefan Mattyasovszky, Martin Weber
No abstract text is available yet for this article.
May 3, 2018: Oncology Research and Treatment
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