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HER2 Inhibition in Gastro-Oesophageal Cancer: a Review Drawing on Lessons Learned from Breast Cancer
Submit a Manuscript: http://www.f6publishing.com World J Gastrointest Oncol 2018 July 15; 10(7): 159-171 DOI: 10.4251/wjgo.v10.i7.159 ISSN 1948-5204 (online) REVIEW HER2 inhibition in gastro-oesophageal cancer: A review drawing on lessons learned from breast cancer Hazel Lote, Nicola Valeri, Ian Chau Hazel Lote, Nicola Valeri, Centre for Molecular Pathology, Accepted: May 30, 2018 Institute of Cancer Research, Sutton SM2 5NG, United Kingdom Article in press: May 30, 2018 Published online: July 15, 2018 Hazel Lote, Nicola Valeri, Ian Chau, Department of Medicine, Royal Marsden Hospital, Sutton SM2 5PT, United Kingdom ORCID number: Hazel Lote (0000-0003-1172-0372); Nicola Valeri (0000-0002-5426-5683); Ian Chau (0000-0003-0286-8703). Abstract Human epidermal growth factor receptor 2 (HER2)- Author contributions: Lote H wrote the original manuscript and revised it following peer review comments; Valeri N reviewed inhibition is an important therapeutic strategy in HER2- the manuscript; Chau I reviewed and contributed to the content of amplified gastro-oesophageal cancer (GOC). A significant the manuscript. proportion of GOC patients display HER2 amplification, yet HER2 inhibition in these patients has not displayed Supported by National Health Service funding to the National the success seen in HER2 amplified breast cancer. Mu- Institute for Health Research Biomedical Research Centre at ch of the current evidence surrounding HER2 has been the Royal Marsden NHS Foundation Trust and The Institute of obtained from studies in breast cancer, and we are only re- Cancer Research, No. A62, No. A100, No. A101 and No. A159; Cancer Research UK funding, No. -
2698 Expression Pattern and Targeting of HER Family Members and IGF-IR In
[Frontiers in Bioscience 17, 2698-2724, June 1, 2012] Expression pattern and targeting of HER family members and IGF-IR in pancreatic cancer Nikolaos Ioannou1, Alan M. Seddon1, Angus Dalgleish2, David Mackintosh1, Helmout Modjtahedi1 1School of Life Sciences, Kingston University London, Kingston, UK, 2Department of Cellular and Molecular Medicine, St George's University of London, London, UK TABLE OF CONTENTS 1. Abstract 2. Introduction 3. HER/ErbB family members and their ligands in pancreatic cancer 3.1. Structure and function of HER/ErbB family members and their ligands 3.2. Expression pattern and prognostic significance of EGFR (HER-1) and its ligands in pancreatic cancer 3.3. Expression pattern and prognostic significance of HER-2 in pancreatic cancer 3.4. Expression pattern and prognostic significance of HER-3 and HER-4 in pancreatic cancer 4. HER family of receptors as therapeutic targets in pancreatic cancer 4.1. EGFR targeting 4.1.1. Anti-EGFR mAbs 4.1.1.1. Cetuximab 4.1.1.2. Panitumumab 4.1.1.3. Matuzumab. 4.1.1.4. Nimotuzumab 4.1.2. EGFR Tyrosine kinase inhibitors 4.1.2.2. Erlotinib 4.1.2.3. Gefitinib 4.2. HER-2 targeting 4.3. HER-3 targeting 4.4. Dual and Pan-HER inhibitors 5. Predictive value of EGFR for response to EGFR inhibitors 6. Mechanisms of resistance to EGFR targeted therapy in pancreatic cancer 6. 1. The role of EGFR mutations in drug resistance. 6. 2. Activation of downstream pathways in an EGFR-independent manner 6. 3. Activation of alternative pathways 7. IGF-IR signalling system in pancreatic cancer 7.1. -
MEDICAL Injectables & ONCOLOGY TREND REPORT™
MEDICAL INJECTABLEs & ONCOLOGY TREND REPORT™ 2010 firsT edition ICORE HEALTHCARE www.ICOREHealthcare.com/Trends.AsPx letter to OuR readers 1 Injectable Drugs: Giving You the Data You Need It is my pleasure to present you with the 2010 ICORE For this first edition, we surveyed 60 medical, pharmacy, and Healthcare Medical Injectables & Oncology Trend clinical directors representing 146 million lives to get an understanding ReportTM. It is the first of what will be an annual of what payors are doing today and planning to do in the future to publication. The purpose of our investment in this manage the quality and cost of care for medical benefit injectables. report is straightforward: Back in 2003 when ICORE We then evaluated health plan medical benefit injectable claims such Healthcare first began assisting payors in managing that benchmarks and trends could be determined. medical injectables, no reference or benchmark data ICORE Healthcare’s mission has not changed in the past seven existed. Frankly, this has continued to be the case years: We serve as the center of medical injectable drug management. until the release of this report, since few, if any, benefit To this end, we believe this report is one additional resource to assist managers are able to review and assess medical benefit our customers, colleagues, and partners. injectable claims. I want to give special thanks to the Assessing medical injectable use, costs, and trends payors who served on our advisory is more critical now than ever, since five of the top board of this publication and 16 drugs in 2009 (based upon sales dollars) were who provided invaluable input specialty drugs, whereas it is expected that 11 drugs of into the report’s overall objective, the top 16 will be injectable or specialty products by content, and design. -
The Role of Epidermal Growth Factor Receptor in Cancer and Their Application Oncology Section for New Targeted Cancer Therapy
DOI: 10.7860/JCDR/2018/35499.11680 Review Article The Role of Epidermal Growth Factor Receptor in Cancer and their Application Oncology Section for New Targeted Cancer Therapy FARAJOLAH MALEKI1, SADEGHIFARD NOORKHODA2, RAHELEH HALABIAN3, ELHAM BEHZADI4, ABBAS ALI IMANI FOOLADI5 ABSTRACT Epidermal Growth Factor Receptor (EGFR) has central role in cancer therapy because it causes tumour progression in many cases. The EGFR has seven ligands. Each factor that can block this binding, inhibits the intracellular signal transduction and prevents progression of the tumours. Immune system response is the most important factor for suppressing the initial stage of tumour growth and destroying some initial malignant cells, daily. On the other hand, tumours have different mechanisms to hide their antigens and escape from immune system responses. In contrary, tumours use some mechanisms to escape from immune system such as: 1) use of TGF-β to initiate angiogenesis and immune suppression; 2) Induces Treg cell activation to modulate other immune cells; 3) secretion of the prostaglandin E2 to convert T cell into Treg. So, if a superantigen fused to one of the EGFR-ligands, causes the induction of immune system responses against the tumour cells. One of the new methods is based on the use of the fused super antigen with a ligand of the EGFR to inhibit ligand attaching to the EGFR and inducing immune system responses. To achieve this goal, we can block binding of EGFR to their ligands in the extracellular domain by fusing ligands with bacterial superantigens, toxins or cytokines of the viruses and plants that can induce immune system responses and kill malignant cells. -
Predictive QSAR Tools to Aid in Early Process Development of Monoclonal Antibodies
Predictive QSAR tools to aid in early process development of monoclonal antibodies John Micael Andreas Karlberg Published work submitted to Newcastle University for the degree of Doctor of Philosophy in the School of Engineering November 2019 Abstract Monoclonal antibodies (mAbs) have become one of the fastest growing markets for diagnostic and therapeutic treatments over the last 30 years with a global sales revenue around $89 billion reported in 2017. A popular framework widely used in pharmaceutical industries for designing manufacturing processes for mAbs is Quality by Design (QbD) due to providing a structured and systematic approach in investigation and screening process parameters that might influence the product quality. However, due to the large number of product quality attributes (CQAs) and process parameters that exist in an mAb process platform, extensive investigation is needed to characterise their impact on the product quality which makes the process development costly and time consuming. There is thus an urgent need for methods and tools that can be used for early risk-based selection of critical product properties and process factors to reduce the number of potential factors that have to be investigated, thereby aiding in speeding up the process development and reduce costs. In this study, a framework for predictive model development based on Quantitative Structure- Activity Relationship (QSAR) modelling was developed to link structural features and properties of mAbs to Hydrophobic Interaction Chromatography (HIC) retention times and expressed mAb yield from HEK cells. Model development was based on a structured approach for incremental model refinement and evaluation that aided in increasing model performance until becoming acceptable in accordance to the OECD guidelines for QSAR models. -
Human EGFR (Research Grade Matuzumab Biosimilar) Antibody
Human EGFR (Research Grade Matuzumab Biosimilar) Antibody Recombinant Monoclonal Human IgG1 Clone # Hu104 Catalog Number: MAB10023 DESCRIPTION Species Reactivity Human Specificity Detects human EGFR based on Matuzumab therapeutic antibody. This non-therapeutic antibody uses the same variable region sequence as the therapeutic antibody Matuzumab. This product is for research use only. Source Recombinant Monoclonal Human IgG1 Clone # Hu104 Purification Protein A or G purified from cell culture supernatant Immunogen Human EGFR Formulation Lyophilized from a 0.2 μm filtered solution in PBS with Trehalose. See Certificate of Analysis for details. *Small pack size (-SP) is supplied either lyophilized or as a 0.2 μm filtered solution in PBS. APPLICATIONS Please Note: Optimal dilutions should be determined by each laboratory for each application. General Protocols are available in the Technical Information section on our website. Recommended Sample Concentration Flow Cytometry 0.25 µg/mL See Below CyTOF-ready Ready to be labeled using established conjugation methods. No BSA or other carrier proteins that could interfere with conjugation. DATA Flow Cytometry Detection of EGF R in A431 human epithelial carcinoma cell line by Flow Cytometry. A431 human epithelial carcinoma cell line was stained with Human Anti-Human EGF R (Research Grade Matuzumab Biosimilar) Monoclonal Antibody (Catalog # MAB10023, filled histogram) or irrelevant antibody (open histogram) followed by APC- conjugated Anti-Human IgG Secondary Antibody (Catalog # F0135). View our protocol for Staining Membrane-associated Proteins. PREPARATION AND STORAGE Reconstitution Reconstitute at 0.5 mg/mL in sterile PBS. Shipping The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature recommended below. -
Nimotuzumab, an Antitumor Antibody That Targets the Epidermal Growth Factor Receptor, Blocks Ligand Binding While Permitting the Active Receptor Conformation
Published OnlineFirst July 7, 2009; DOI: 10.1158/0008-5472.CAN-08-4518 Experimental Therapeutics, Molecular Targets, and Chemical Biology Nimotuzumab, an Antitumor Antibody that Targets the Epidermal Growth Factor Receptor, Blocks Ligand Binding while Permitting the Active Receptor Conformation Ariel Talavera,1,2 Rosmarie Friemann,2,3 Silvia Go´mez-Puerta,1 Carlos Martinez-Fleites,4 Greta Garrido,1 Ailem Rabasa,1 Alejandro Lo´pez-Requena,1 Amaury Pupo,1 Rune F. Johansen,3 Oliberto Sa´nchez,5 Ute Krengel,2 and Ernesto Moreno1 1Center of Molecular Immunology, Havana, Cuba; 2Department of Chemistry, University of Oslo, Oslo, Norway; and 3Center for Molecular and Behavioral Neuroscience, Institute of Medical Microbiology, University of Oslo, Rikshospitalet HF, Oslo, Norway; 4Department of Chemistry, University of York, Heslington, York, United Kingdom; and 5Center for Genetic Engineering and Biotechnology, Havana, Cuba Abstract region of the EGFR (eEGFR), leaving the dimerization ‘‘arm’’ in Overexpression of the epidermal growth factor (EGF) receptor domain II ready for binding a second monomer (4, 5). It has been (EGFR) in cancer cells correlates with tumor malignancy and shown that the eEGFR adopts a ‘‘tethered’’ or inactive conformation poor prognosis for cancer patients. For this reason, the EGFR in the absence of EGF (6). In this characteristic conformation, has become one of the main targets of anticancer therapies. the dimerization arm is hidden by interactions with domain IV, Structural data obtained in the last few years have revealed whereas domains I and III remain separated. Thus, to adopt the the molecular mechanism for ligand-induced EGFR dimeriza- ‘‘extended’’ or active conformation observed in the crystal structure tion and subsequent signal transduction, and also how this of the complex with EGF (4), the receptor must undergo a major signal is blocked by either monoclonal antibodies or small conformational change that brings together domains I and III (6). -
Activating Death Receptor DR5 As a Therapeutic Strategy for Rhabdomyosarcoma
International Scholarly Research Network ISRN Oncology Volume 2012, Article ID 395952, 10 pages doi:10.5402/2012/395952 Review Article Activating Death Receptor DR5 as a Therapeutic Strategy for Rhabdomyosarcoma Zhigang Kang,1, 2 Shi-Yong Sun,3 and Liang Cao1 1 Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA 2 Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc., NCI Frederick, Frederick, MD 21702, USA 3 Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA Correspondence should be addressed to Liang Cao, [email protected] Received 4 January 2012; Accepted 24 January 2012 Academic Editors: E. Boven and S. Mandruzzato Copyright © 2012 Zhigang Kang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. It is believed to arise from skeletal muscle progenitors, preserving the expression of genes critical for embryonic myogenic development such as MYOD1 and myogenin. RMS is classified as embryonal, which is more common in younger children, or alveolar, which is more prevalent in elder children and adults. Despite aggressive management including surgery, radiation, and chemotherapy, the outcome for children with metastatic RMS is dismal, and the prognosis has remained unchanged for decades. Apoptosis is a highly regulated process critical for embryonic development and tissue and organ homeostasis. Like other types of cancers, RMS develops by evading intrinsic apoptosis via mutations in the p53 tumor suppressor gene. -
Or Ramucirumab (IMC-1121B) Plus Mitoxantrone and Prednisone in Men with Metastatic Docetaxel-Pretreated Castration-Resistant Prostate Cancer
European Journal of Cancer (2015) 51, 1714– 1724 Available at www.sciencedirect.com ScienceDirect journal homepage: www.ejcancer.com A randomised non-comparative phase II trial of cixutumumab (IMC-A12) or ramucirumab (IMC-1121B) plus mitoxantrone and prednisone in men with metastatic docetaxel-pretreated castration-resistant prostate cancer Maha Hussain a,1,⇑, Dana Rathkopf b,1, Glenn Liu c,1, Andrew Armstrong d,1, Wm. Kevin Kelly e, Anna Ferrari f, John Hainsworth g, Adarsh Joshi h, Rebecca R. Hozak i, Ling Yang h, Jonathan D. Schwartz h,2, Celestia S. Higano j,1 a University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, United States b Memorial Sloan-Kettering, New York, NY, United States c University of Wisconsin, Carbone Cancer Center, Madison, WI, United States d Duke Cancer Institute and Duke Prostate Center, Duke University, Durham, NC, United States e Thomas Jefferson University, Philadelphia, PA, United States f New York University Clinical Cancer Center, New York, NY, United States g Sarah Cannon Research Institute, Nashville, TN, United States h Eli Lilly and Company, Bridgewater, NJ, United States i Eli Lilly and Company, Indianapolis, IN, United States j University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA, United States Received 11 February 2015; received in revised form 27 April 2015; accepted 10 May 2015 Available online 13 June 2015 KEYWORDS Abstract Background: Cixutumumab, a human monoclonal antibody (HuMAb), targets the Ramucirumab insulin-like growth factor receptor. Ramucirumab is a recombinant HuMAb that binds to vas- Cixutumumab cular endothelial growth factor receptor-2. A non-comparative randomised phase II study Mitoxantrone evaluated cixutumumab or ramucirumab plus mitoxantrone and prednisone (MP) in Prednisone metastatic castration-resistant prostate cancer (mCRPC). -
Targeted and Novel Therapy in Advanced Gastric Cancer Julie H
Selim et al. Exp Hematol Oncol (2019) 8:25 https://doi.org/10.1186/s40164-019-0149-6 Experimental Hematology & Oncology REVIEW Open Access Targeted and novel therapy in advanced gastric cancer Julie H. Selim1 , Shagufta Shaheen2 , Wei‑Chun Sheu3 and Chung‑Tsen Hsueh4* Abstract The systemic treatment options for advanced gastric cancer (GC) have evolved rapidly in recent years. We have reviewed the recent data of clinical trial incorporating targeted agents, including inhibitors of angiogenesis, human epidermal growth factor receptor 2 (HER2), mesenchymal–epithelial transition, epidermal growth factor receptor, mammalian target of rapamycin, claudin‑18.2, programmed death‑1 and DNA. Addition of trastuzumab to platinum‑ based chemotherapy has become standard of care as front‑line therapy in advanced GC overexpressing HER2. In the second‑line setting, ramucirumab with paclitaxel signifcantly improves overall survival compared to paclitaxel alone. For patients with refractory disease, apatinib, nivolumab, ramucirumab and TAS‑102 have demonstrated single‑agent activity with improved overall survival compared to placebo alone. Pembrolizumab has demonstrated more than 50% response rate in microsatellite instability‑high tumors, 15% response rate in tumors expressing programmed death ligand 1, and non‑inferior outcome in frst‑line treatment compared to chemotherapy. This review summarizes the current state and progress of research on targeted therapy for advanced GC. Keywords: Gastric cancer, Targeted therapy, Human epidermal growth factor receptor 2, Programmed death‑1, Vascular endothelial growth factor receptor 2 Background GC mortality which is consistent with overall decrease in Gastric cancer (GC), including adenocarcinoma of the GC-related deaths [4]. gastroesophageal junction (GEJ) and stomach, is the ffth Tere have been several eforts to perform large-scale most common cancer and the third leading cause of can- molecular profling and classifcation of GC. -
Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix
United States International Trade Commission Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix USITC Publication 4208 December 2010 U.S. International Trade Commission COMMISSIONERS Deanna Tanner Okun, Chairman Irving A. Williamson, Vice Chairman Charlotte R. Lane Daniel R. Pearson Shara L. Aranoff Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix Publication 4208 December 2010 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 15, 2010, set forth at the end of this publication, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the United States International Trade Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement changes to the Pharmaceutical Appendix, effective on January 1, 2011. Table 1 International Nonproprietary Name (INN) products proposed for addition to the Pharmaceutical Appendix to the Harmonized Tariff Schedule INN CAS Number Abagovomab 792921-10-9 Aclidinium Bromide 320345-99-1 Aderbasib 791828-58-5 Adipiplon 840486-93-3 Adoprazine 222551-17-9 Afimoxifene 68392-35-8 Aflibercept 862111-32-8 Agatolimod -
Tanibirumab (CUI C3490677) Add to Cart
5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor