ARID1A mutations in lung cancer: biology,prognostic role,and therapeutic implications |
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| Institution: | 1. JCCU Translational Surgical Oncology (A430), German Cancer Research Center (DKFZ), Heidelberg, Germany;2. DKFZ-Hector Cancer Institute, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;3. Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;4. Department of Thoracic Surgery, The First Hospital of Jilin University, Jilin, China;5. Division of Personalized Medical Oncology (A420), German Cancer Research Center (DKFZ), Heidelberg, Germany;6. Department of Personalized Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;1. Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH-Alliance, Heidelberg, Germany;2. School of Life Sciences, Tsinghua University, Beijing 100084, China;3. Institute for Plant Sciences, Cluster of Excellence on Plant Sciences (CEPLAS), University of Cologne, Cologne, Germany;4. Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA;5. Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Jena, Germany;6. Department of Biology, Washington University in St. Louis, St. Louis, MO, USA;1. Vall d’Hebron Research Institute (VHIR). Universitat Autónoma de Barcelona, Barcelona, 08035, Spain;2. Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, 03010, Spain;3. Instituto de Neurosciencias CSIC-UMH, San Juan de Alicante, 03550, Spain;1. Department of Pediatrics, Division of Pediatric Hematology-Oncology, Hassenfeld Children''s Hospital at NYU Langone Health, NYU Grossman School of Medicine, New York, NY, USA;2. Division of Hematology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;3. Dana-Farber/Boston Children''s Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA, USA;1. Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON M5G 1L7, Canada;2. Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama 700-8558, Japan;3. Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada;4. Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A8, Canada;5. Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada;6. Division of Rheumatology, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada;1. Translational Research Centre in Oncohaematology, Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland;2. Institute of Life Sciences and Biomedicine, Far Eastern Federal University, 690090 Vladivostok, Russia;3. College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian 350108, China;4. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina Str., Moscow 117997, Russia;5. Department of Functional Biochemistry of Biopolymers, A.N. Belozersky Research Institute of Physico-Chemical Biology, Moscow State University, 119992 Moscow, Russia;1. Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, 4200-135 Porto, Portugal;2. Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, 4200-135 Porto, Portugal;3. Department of Biological Sciences, Faculty of Pharmacy of the University of Porto (FFUP), Porto, Portugal;4. Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands;5. Fondazione Pisana per La Scienza, Pisa, Italy |
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| Abstract: | Mutations in the AT-interacting domain-rich protein 1A (ARID1A) gene, a critical component of the switch/sucrose nonfermentable (SWI/SNF) complex, are frequently found in most human cancers. Approximately 5–10% of lung cancers carry ARID1A mutations. ARID1A loss in lung cancer correlates with clinicopathological features and poor prognosis. Co-mutation of ARID1A and epidermal growth factor receptor (EGFR) results in the limited efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) but increases the clinical benefit of immune checkpoint inhibitors (ICIs). ARID1A gene mutation plays a role in cell cycle regulation, metabolic reprogramming, and epithelial–mesenchymal transition. We present the first comprehensive review of the relationship between ARID1A gene mutations and lung cancer and discuss the potential of ARID1A as a new molecular target. |
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