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Martyn E Caplin Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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Marianne Pavel Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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Jarosław B Ćwikła Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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Alexandria T Phan Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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Markus Raderer Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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Eva Sedláčková Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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Guillaume Cadiot Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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Edward M Wolin Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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Jaume Capdevila Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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Lucy Wall Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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Guido Rindi Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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Alison Langley Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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Séverine Martinez Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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Edda Gomez-Panzani Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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Philippe Ruszniewski Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK
Royal Free Hospital, Charité University Medicine Berlin, University of Warmia and Mazury, University of Texas MD Anderson Cancer Center, University Hospital, Department of Oncology of the First Faculty of Medicine and General Teaching Hospital, Robert‐Debré Hospital, Markey Cancer Center, Vall d'Hebron University Hospital, Western General Hospital, Università Cattolica del Sacro Cuore, Ipsen, Ipsen, Beaujon Hospital, Paris Diderot University, London, UK

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on behalf of the CLARINET Investigators
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neoplasia; or previous cancer (except in situ cervical or uterine carcinoma or basal-cell skin carcinoma or other cancers treated with curative intent and disease-free for >5 years). Patients were eligible for the OLE study if attending a participating

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Tobias Hofving Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Viktor Sandblom Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Yvonne Arvidsson Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Emman Shubbar Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Gülay Altiparmak Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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John Swanpalmer Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden

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Bilal Almobarak Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Anna-Karin Elf Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Viktor Johanson Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Erik Elias Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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Erik Kristiansson Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden

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Eva Forssell-Aronsson Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden

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Ola Nilsson Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

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/β. 177 Lu-octreotate therapy was enhanced by heat shock protein inhibition in the GOT1 xenograft First-generation Hsp90 inhibitors have been shown to sensitise cancer cells to radiation ( Dote et al. 2006 , Lauber et al. 2015 , Wang et al

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Jaydira Del Rivero Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, USA

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Josh Mailman NorCal CarciNET Community, Oakland, California, USA

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Michael W Rabow Department of Internal Medicine, Division of Palliative Medicine, University of California, San Francisco, San Francisco, California, USA

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Jennifer A Chan Harvard Medical School, Program in Carcinoid and Neuroendocrine Tumors, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

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Sarah Creed Good Shepherd Community Care, Harvard Kennedy School, Natick, Massachusetts, USA

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Hagen F Kennecke Providence Cancer Institute Franz Clinic, Portland Providence Medical Center, Portland, Oregon, USA

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Janice Pasieka Department of Surgery, Section of General Surgery, University of Calgary, Cumming School of Medicine, Calgary, Canada

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Jennifer Zuar Department of Internal Medicine, Division of Geriatrics and Palliative Medicine, Alpert Medical School, Providence, Rhode Island, USA

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Simron Singh Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

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Lauren Fishbein Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, Department of Biomedical Informatics, University of Colorado School of Medicine, Aurora, Colorado, USA

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larger approach to care and should be offered to those at any point in their cancer journey. Hospice differs from palliative care since it provides care specifically at the end of life and in a place which a patient calls home, be it a private residence

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Paula Fontes Asprino Hospital Sírio-Libanês (HSL), São Paulo, São Paulo, Brazil

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Rudinei Diogo Marques Linck Hospital Sírio-Libanês (HSL), São Paulo, São Paulo, Brazil
Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, São Paulo, Brazil

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Jônatas Cesar Instituto de Biociências – Universidade de São Paulo (IB-USP), São Paulo, São Paulo, Brazil

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Florêncio Porto Freitas Hospital Sírio-Libanês (HSL), São Paulo, São Paulo, Brazil

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Fernanda Christtanini Koyama Hospital Sírio-Libanês (HSL), São Paulo, São Paulo, Brazil

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Rachel Simões Pimenta Riechelmann Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, São Paulo, Brazil

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Frederico Perego Costa Hospital Sírio-Libanês (HSL), São Paulo, São Paulo, Brazil

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Paulo Marcelo Gehm Hoff Hospital Sírio-Libanês (HSL), São Paulo, São Paulo, Brazil
Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, São Paulo, Brazil

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Pedro Alexandre Favoretto Galante Hospital Sírio-Libanês (HSL), São Paulo, São Paulo, Brazil

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Diogo Meyer Instituto de Biociências – Universidade de São Paulo (IB-USP), São Paulo, São Paulo, Brazil

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Anamaria Aranha Camargo Hospital Sírio-Libanês (HSL), São Paulo, São Paulo, Brazil

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Jorge Sabbaga Hospital Sírio-Libanês (HSL), São Paulo, São Paulo, Brazil
Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, São Paulo, Brazil

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Hospital Sírio-Libanês or at Instituto do Câncer do Estado de São Paulo were enrolled in this study. All patients provided written informed consent, and the study was approved by the ethics committees of both institutions (HSL2015-15 and NP762

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Adel Mandl Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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James M Welch Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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Gayathri Kapoor Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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Vaishali I Parekh Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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David S Schrump Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA

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R Taylor Ripley Division of General Thoracic Surgery, Baylor College of Medicine, Houston, Texas, USA

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Mary F Walter NIDDK Clinical Core, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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Jaydira Del Rivero Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA

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Smita Jha Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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William F Simonds Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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Robert T Jensen Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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Lee S Weinstein Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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Jenny E Blau Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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Sunita K Agarwal Metabolic Diseases Branch, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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). KSR2 has been reported to play a role in many diseases including early onset obesity, metabolic syndrome, insulin resistance, non-small cell lung cancer, melanoma, endometrial cancer, and invasive ductal carcinoma of the breast. Potential targeted

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Maria Angela De Stefano Department of Public Health, University of Naples ’Federico II’, Naples, Italy

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Tommaso Porcelli Department of Public Health, University of Naples ’Federico II’, Naples, Italy

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Raffaele Ambrosio IRCCS SDN, Naples, Italy

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Cristina Luongo Department of Clinical Medicine and Surgery, University of Naples ’Federico II’, Naples, Italy

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Maddalena Raia CEINGE Biotecnologie Avanzate Scarl, Naples, Italy

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Martin Schlumberger Department of Endocrine Oncology, Gustave Roussy and University Paris-Saclay, Villejuif, France

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Domenico Salvatore Department of Public Health, University of Naples ’Federico II’, Naples, Italy
CEINGE Biotecnologie Avanzate Scarl, Naples, Italy

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Introduction Anaplastic thyroid cancer (ATC) is a rare, aggressive tumor that accounts for only 1% of all thyroid cancers, but it is responsible for about one-third of all deaths from thyroid cancer ( Fagin & Wells 2016 ). ATC originates from

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Maria Angela De Stefano Department of Public Health, University of Naples “Federico II”, Naples, Italy

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Tommaso Porcelli Department of Public Health, University of Naples “Federico II”, Naples, Italy

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Martin Schlumberger Department of Endocrine Oncology, Gustave Roussy and University Paris-Saclay, Villejuif, France

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Domenico Salvatore Department of Public Health, University of Naples “Federico II”, Naples, Italy
CEINGE Biotecnologie Avanzate Scarl, Naples, Italy

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for the induction of differentiation muscle genes ( Dentice et al. 2014 , Ambrosio et al. 2017 ). Modulation of deiodinase expression also occurs in several cancers vs their normal corresponding tissues ( Nappi et al. 2021 ). Increased

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Adam I Kaplan Kolling Institute of Medical Research, The University of Sydney, Sydney, Australia
Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia

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Trisha Dwight Cancer Genetics Laboratory, Kolling Institute, Royal North Shore Hospital, Sydney, Australia
Faculty of Medicine and Health, The University of Sydney, Sydney, Australia

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Catherine Luxford Cancer Genetics Laboratory, Kolling Institute, Royal North Shore Hospital, Sydney, Australia
Faculty of Medicine and Health, The University of Sydney, Sydney, Australia

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Diana E Benn Cancer Genetics Laboratory, Kolling Institute, Royal North Shore Hospital, Sydney, Australia
Faculty of Medicine and Health, The University of Sydney, Sydney, Australia

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Roderick J Clifton-Bligh Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia
Cancer Genetics Laboratory, Kolling Institute, Royal North Shore Hospital, Sydney, Australia
Faculty of Medicine and Health, The University of Sydney, Sydney, Australia

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through the mitochondrial respiratory chain leads to increased reactive oxygen species (ROS) such as superoxides, which are known drivers of proliferation in various forms of cancer ( Bénit et al. 2022 ). Secondly, succinate accumulation inhibits several

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Tobias Hofving Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Yvonne Arvidsson Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Bilal Almobarak Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Linda Inge Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Roswitha Pfragner Institute of Pathophysiology and Immunology, Center for Molecular Medicine, Medical University of Graz, Graz, Austria

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Marta Persson Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Göran Stenman Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Erik Kristiansson Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden

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Viktor Johanson Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Ola Nilsson Sahlgrenska Cancer Center, Department of Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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repair gene CHEK2 showed a homozygous mutation in BON-1. Finally, we studied other cancer-associated genes, by analysing the 127 mutated genes identified in the Tumor Cancer Genome Atlas (TCGA) Pan-Cancer effort. ( Kandoth et al . 2013 ) Out of these

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Samuel M O’Toole William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK
Department of Endocrinology, St Bartholomew’s Hospital, Barts Health NHS Trust, London, UK

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David S Watson William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK

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Tatiana V Novoselova William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK

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Lisa E L Romano William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK

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Peter J King William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK

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Teisha Y Bradshaw William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK

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Clare L Thompson Institute of Bioengineering and School of Engineering and Material Sciences, Queen Mary University of London, London, UK

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Martin M Knight Institute of Bioengineering and School of Engineering and Material Sciences, Queen Mary University of London, London, UK

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Tyson V Sharp Barts Cancer Institute, Queen Mary University of London, London, UK

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Michael R Barnes William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK

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Umasuthan Srirangalingam William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK
Department of Endocrinology, St Bartholomew’s Hospital, Barts Health NHS Trust, London, UK
Department of Diabetes and Endocrinology, University College London Hospital, London, UK

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William M Drake Department of Endocrinology, St Bartholomew’s Hospital, Barts Health NHS Trust, London, UK

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J Paul Chapple William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK

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. 2016 ). Understanding of the pathogenesis of PCC/PGLs is incomplete, with limited ability to predict malignant potential and at present the response to conventional cancer therapies is disappointing. Approximately 30% of PCC/PGLs are associated with

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