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Xuzhi He, Jazmina L Cruz, Shannon Joseph, Nicola Pett, Hui Yi Chew, Zewen K Tuong, Satomi Okano, Gabrielle Kelly, Margaret Veitch, Fiona Simpson, James W Wells
The Epidermal Growth Factor Receptor (EGFR) is selectively expressed on the surface of numerous tumours, such as non-small cell lung, ovarian, colorectal and head and neck carcinomas. EGFR has therefore become a target for cancer therapy. Cetuximab is a chimeric human/mouse monoclonal antibody (mAb) that binds to EGFR, where it both inhibits signaling and induces cell death by antibody-dependent cell mediated cytotoxicity (ADCC). Cetuximab has been approved for clinical use in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal cancer...
February 23, 2018: Oncotarget
Haohua Wang, Roujun Peng, Xiuxing Chen, Rui Jia, Chunyue Huang, Yuanyuan Huang, Liangping Xia, Guifang Guo
Although hexokinase (HK) 2, pyruvate kinase muscle (PKM) isozyme 2 and lactate dehydrogenase (LDH) A predict the efficacy of medicines in various solid tumors, their ability to predict the efficacy of cetuximab in metastatic colorectal cancer (mCRC) remains unclear. mCRC patients with pathological specimens who received cetuximab and chemotherapy from 2005 to 2015 in the present institution were enrolled. Immunohistochemistry was used to detect HK2, PKM2 and LDHA expression. SPSS20 was used for statistical analysis...
April 2018: Oncology Letters
Chuandong Zhu, Lixue Wang, Yang Cai, Guoxiang Wang, Hanfeng Xu, Yuan Wan, Qin Zheng
The high atomic number of gold nanoparticles (GNPs) enables them to offer potential as practical and efficient radiosensitizing agents for cancer radiotherapy applications. In the present study, it was demonstrated that GNPs can significantly modulate the irradiation response of hepatocellular carcinoma (HCC) cells in vitro and in vivo , of which the underlying mechanisms were investigated. Cetuximab (C225) is a targeting agent, which binds to the extracellular domain of epidermal growth factor receptor (EGFR)...
April 2018: Oncology Letters
Qiushi Sun, Yuan Liu, Bo Liu, Yingying Liu
BACKGROUND: Patients with colorectal cancer (CRC) who are sensitive to epidermal growth factor antibodies inevitably acquire drug resistance. This study aimed to determine the usefulness of liquid biopsies for prognosis and clinical correlation. MATERIALS AND METHODS: For liquid biopsy tests, we extracted blood from 140 CRC patients with matched tumor samples. Circulating tumor cells (CTCs) and tumor DNA (ctDNA) were extracted before surgery and treatment. Samples were quantified and tested for mutations in KRAS, NRAS and BRAF...
March 2018: American Journal of the Medical Sciences
Leena Chularojanamontri, Papapit Tuchinda, Chayanee Likitwattananurak, Kamolwan Pongparit, Chuda Rujitharanawong, Suthinee Ithimakin, Kanokvalai Kulthanan
BACKGROUND: Several prospective studies have been conducted in epidermal growth factor receptor (EGFR) inhibitor-related cutaneous reactions in Caucasian patients, but prospective studies in Asian populations are scarce. OBJECTIVE: To investigate the cutaneous side effects of EGFR inhibitors in Asian cancer patients and to assess tumor response to dermatologic manifestations. METHODS: Sixty patients with lung or colorectal cancer who were receiving EGFR inhibitors were prospectively followed for at least one year by oncologists and dermatologists...
March 12, 2018: Asian Pacific Journal of Allergy and Immunology
Nelson S Yee
Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented a variety of topics that focused on this sub-specialty. This conference paper highlights the new development in systemic treatment of various malignant diseases in the digestive system. Results of the recent clinical trials that investigated the clinical efficacy of pegylated hyaluronidase, napabucasin, and L-asparaginase in pancreatic carcinoma are presented...
March 16, 2018: Biomedicines
Jitendrakumar Patel, Jitendra Amrutiya, Priyanka Bhatt, Ankit Javia, Mukul Jain, Ambikanandan Misra
Aim of this study was to develop anti EGFR antibody conjugated poly (lactide-co-glycolide) nanoparticles (NPs) to target epidermal growth factor receptor, highly expressed on non-small cell lung cancer cells to improve cytotoxicity and site specificity. Cetuximab was conjugated to Docetaxel loaded PLGA NPs by known EDC/NHS chemistry and characterized for size, zeta potential, conjugation efficiency and results were 128.4 ±3.6 nm, -31.0 ± 0.8 mV and 39.77 ± 3.4% respectively. In-vitro release study demonstrated sustained release of drug from NPs with 25% release at pH 5...
March 15, 2018: Journal of Microencapsulation
Sagus Sampath, Haejung Won, Erminia Massarelli, Min Li, Paul Frankel, Nayana Vora, Lalit Vora, Ellie Maghami, Marcin Kortylewski
Immunomodulation contributes to the antitumor efficacy of the fractionated radiation therapy (RT). Here, we describe immune effects of RT with concurrent systemic cisplatin or cetuximab treatment of patients with stage III-IV head and neck squamous cell carcinoma (HNSCC). Using longitudinally collected blood samples, we identified significant changes in cytokines/chemokines and immune cell populations compared to immune-related gene expression profiles in peripheral blood mononuclear cells (PBMCs). The 7-week combinatorial RT resulted in gradual elevation of proinflammatory mediators (IFNγ, IL-6, TNFɑ, CCL2), while levels of IL-12, cytokine essential for antitumor immune responses, were decreased...
February 16, 2018: Oncotarget
Guangzhong Xu, Kai Li, Nengwei Zhang, Bin Zhu, Guosheng Feng, Qing Fan
Colorectal cancer is a common malignancy with a high prevalence and associated mortality rate. However, the preclinical tools currently used for drug development are insufficient. The aim of the present study was to establish and characterize a specific patient-derived colon cancer xenograft (PDCCX) mouse model for drug testing. Primary colon tumors were obtained from 10 patients by surgical resection, and tumor tissues were subsequently grafted into nude mice followed by consecutive passages. Primary tumors and xenograft tumors were collected and processed for DNA sequencing, histological evaluation and immunohistochemical staining...
April 2018: Oncology Letters
Wenjie Dong, Na Li, Xiufeng Pei, Xinai Wu
Dual-specificity phosphatase-2 (DUSP2), a negative regulator of extracellular-regulated kinase activity, has been identified as an important kinase with emerging roles in cancer. However, the clinical significance of DUSP2 in colorectal cancer (CRC) remains to be fully elucidated. In the present study, the expression of DUSP2 was investigated using immunohistochemistry in 96 patients with CRC. Cell viability was estimated using a cell counting kit-8 assay, and cell apoptosis by flow cytometry. The relationship between DUSP2 expression and patient characteristics, including overall survival, were studied retrospectively in these patients...
April 2018: Oncology Letters
Vanessa Trieu, Harlan Pinto, Jonathan W Riess, Ruth Lira, Richard Luciano, Jessie Coty, Derek Boothroyd, A Dimitrios Colevas
LESSONS LEARNED: Chemotherapy for recurrent, metastatic squamous cell carcinoma of the head and neck need not be known for extreme toxicity.The weekly regimen studied here has been demonstrated to be tolerable and effective. BACKGROUND: The objective of this study was to establish the response rate, progression-free survival (PFS) and overall survival (OS), and safety profile of weekly docetaxel, platinum, and cetuximab (TPC) in patients with relapsed or metastatic squamous cell carcinoma of the head and neck (SCCHN)...
March 14, 2018: Oncologist
Shanshan Sun, Yansheng Wu, Wenyu Guo, Feng Yu, Lingping Kong, Yu Ren, Yu Wang, Xiaofeng Yao, Chao Jing, Chao Zhang, Mingyang Liu, Yuqing Zhang, Minghui Zhao, Zhaoqing Li, Chuanqiang Wu, Yu Qiao, Jingxuan Yang, Xudong Wang, Lun Zhang, Min Li, Xuan Zhou
PURPOSE: Phosphotidylinositol-3-kinase (PI3K)and signal transducers and activators of transcription 3 (STAT3) are frequently activated in cancer progression. However, little is known about the underlying mechanisms by which PI3K and STAT3 regulate HNSCC growth. The lncRNA HOX transcript antisense RNA (HOTAIR) was found to modulate the progression of head and neck squamous cell cancer (HNSCC). In this study, we attempted to establish the correlation of PI3K-STAT3-HOTAIR signaling with the progression of HNSCC and its sensitivity towards platinum-based and targeted anti-EGFR combination therapy...
March 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
HaYeon Kim, John A Vargo, Sushil Beriwal, David A Clump, James P Ohr, Robert L Ferris, Dwight E Heron, M Saiful Huq, Kenneth J Smith
BACKGROUND: The purpose of this study was to present our evaluation of the cost-effectiveness of salvage therapies for patients with recurrent head and neck cancer. METHODS: A Markov model was developed with 5 salvage treatment strategies: (1) platinum-based chemotherapy alone; (2) chemotherapy plus cetuximab; (3) stereotactic body radiotherapy (SBRT) alone; (4) SBRT plus cetuximab; and (5) intensity-modulated radiotherapy (IMRT) plus chemotherapy. Clinical parameters were obtained from comprehensive literature review and 2016 Medicare reimbursement...
March 14, 2018: Head & Neck
Luca Mazzarella, Alessandro Guida, Giuseppe Curigliano
Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials...
March 14, 2018: Expert Opinion on Biological Therapy
Zhenhua Wu, Mingzhu Huang, Yiwei Gong, Chen Lin, Weijian Guo
Mutations in the oncogene BRAF(V600E) are found in ~10% of colorectal cancers (CRCs) and are associated with poor prognosis. However, BRAF(V600E) has a limited response to the small-molecule drug, vemurafenib, a BRAF inhibitor, and BRAF inhibition is thought to cause a feedback activation of EGFR signaling that supports continued proliferation. In this study, we explored the effect of combined use of dabrafenib, a BRAF inhibitor, and cetuximab, an EGFR inhibitor, on BRAF(V600E)-mutant CRC stem cells and its possible mechanisms...
March 9, 2018: Acta Biochimica et Biophysica Sinica
Chiara Cremolini, Massimo Milione, Federica Marmorino, Federica Morano, Gemma Zucchelli, Alessia Mennitto, Michele Prisciandaro, Sara Lonardi, Alessio Pellegrinelli, Daniele Rossini, Francesca Bergamo, Giuseppe Aprile, Lucio Urbani, Luca Morelli, Marta Schirripa, Giovanni Gerardo Cardellino, Matteo Fassan, Gabriella Fontanini, Filippo de Braud, Vincenzo Mazzaferro, Alfredo Falcone, Filippo Pietrantonio
BACKGROUND: Many factors, including histopathologic parameters, seem to influence the prognosis of patients undergoing resection of colorectal cancer liver metastases (CRCLM), although their relative weight is unclear. Histopathologic growth patterns (HGPs) of CRCLM may affect sensitivity to antiangiogenics. We aimed at evaluating differences in histopathologic parameters of response according to the use of bevacizumab or cetuximab as first-line targeted agents, and at exploring the prognostic and predictive role of HGPs...
March 13, 2018: British Journal of Cancer
Maxine D Fisher, Ancilla W Fernandes, Temitope O Olufade, Paul J Miller, Mark S Walker, Moon Fenton
PURPOSE: The goal of this study was to describe patient characteristics, health resource utilization (HRU), and costs associated with treating recurrent or refractory head and neck cancer (HNC) among patients with disease progression in the community oncology setting. METHODS: This retrospective observational study was conducted by using data from the Vector Oncology Data Warehouse. Patients had been diagnosed with locally advanced or metastatic (stage III-IVc) HNC between January 1, 2007, and October 1, 2015...
March 9, 2018: Clinical Therapeutics
Tong Wang, Fumou Sun, Yang Wang, Jiahao Jiang, Mingzhu Pan, Minne Yuan, Hang Zhang, Xiaodian Du, Kamal Hezam, Kai Song, Min Wang, Juan Zhang
Colorectal carcinoma (CRC) is one of the most common malignant cancers worldwide. The poor response of CRC to chemotherapy has whipped up the interest in targeted therapy with monoclonal antibodies for its potential efficiency. However, cetuximab, as one of the first-line targeted drugs in the treatment of CRC, has drug resistance and poor prognosis in clinic. To address this, a novel bispecific protein with CRC targeting and natural killer (NK) cell triggering was used for treatment. NK cell-mediated immunosurveillance is normally activated by the activating receptor natural killer cell receptor NK group 2, member D (NKG2D), which binds its key ligand major histocompatibility complex (MHC) class I-related chain A (MICA) expressed on the tumor cells...
April 2018: Journal of Immunotherapy
Carminia Maria Della Corte, Vincenza Ciaramella, Claudia Cardone, Silvia La Monica, Roberta Alfieri, Pier Giorgio Petronini, Umberto Malapelle, Elena Vigliar, Francesco Pepe, Giancarlo Troncone, Maria Domenica Castellone, Teresa Troiani, Erika Martinelli, Fortunato Ciardiello, Floriana Morgillo
HYPOTHESIS: Osimertinib showed great clinical efficacy for activated-EGFR-NSCLC patients treatment. The aim of this work was to test the efficacy of a complete EGFR-inhibition by osimertinib plus the monoclonal antibody, cetuximab, or the MEK1/2-inhibitor, selumetinib, in EGFR-mutated-NSCLC in vivo models. METHODS: We evaluated combinations of osimertinib plus selumetinib/cetuximab in HCC827 (E746-A759del/T790M-), H1975 (L858R/T790M+) and PC9-T790M (E746-A759del /T790M+) xenografts, in second-line after the developing of resistance to osimertinib and in first-line, and we explored mechanisms of resistance to these treatments...
March 8, 2018: Journal of Thoracic Oncology
Magali Rouyer, Eric François, Antonio Sa Cunha, Alain Monnereau, Pernelle Noize, Philip Robinson, Cécile Droz-Perroteau, Alise Le Monies de Sagazan, Jérémy Jové, Régis Lassalle, Nicholas Moore, Annie Fourrier-Réglat, Denis Smith
INTRODUCTION: Few real-life data are available on cetuximab benefit. The EREBUS cohort was performed to assess metastases resection rate, use, safety, and survival outcomes in wild-type KRAS (Kirsten rat sarcoma viral oncogene) patients with initially unresectable metastatic colorectal cancer (mCRC) treated by cetuximab in real practice. PATIENTS AND METHODS: The study cohort comprised patients initiating cetuximab between January 2009 and December 2010 in 65 French centers, with initially unresectable mCRC and wild-type KRAS...
January 31, 2018: Clinical Colorectal Cancer
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