Pharmacological Targeting of IRE1 in Cancer
| Autor: | Dimitrios Doultsinos, Eric Chevet, Antonio Carlesso, Diana Pelizzari Raymundo, Xavier Guillory, Leif A. Eriksson |
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| Přispěvatelé: | Jonchère, Laurent, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Gothenburg (GU), This work was funded by grants from Institut National du Cancer (INCa PLBIO), Fondation pour la Recherche Médicale (FRM, équipe labellisée 2018), ERANET , and Agence Nationale de la Recherche (ERAAT) to E.C., EU H2020 MSCA ITN-675448 (TRAINERS), and MSCA RISE-734749 (INSPIRED) provided grants to L.A.E. and E.C. D.P.R. was funded by INSERM (LA VANNETAISE). X.G. was funded by a post-doctoral fellowship from Fondation ARC , and D.D. and A.C. were MSCA ITN fellows (TRAINERS)., Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA) |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research [SDV.CAN]Life Sciences [q-bio]/Cancer Context (language use) IRE1 Protein Serine-Threonine Kinases Inositol-requiring enzyme 1 Bioinformatics 03 medical and health sciences 0302 clinical medicine Allosteric Regulation Protein Domains [SDV.CAN] Life Sciences [q-bio]/Cancer Neoplasms Antineoplastic Combined Chemotherapy Protocols Endoribonucleases inhibitors Humans Medicine Mode of action Protein Kinase Inhibitors activators business.industry Cancer unfolded protein response Endoplasmic Reticulum Stress medicine.disease 3. Good health Gene Expression Regulation Neoplastic endoplasmic reticulum 030104 developmental biology Oncology Protein kinase domain 030220 oncology & carcinogenesis Proteostasis Unfolded protein response business Signal Transduction |
| Zdroj: | Trends in Cancer Trends in Cancer, 2020, 6 (12), pp.1018-1030. ⟨10.1016/j.trecan.2020.07.006⟩ Trends in Cancer, Cell Press, 2020, 6 (12), pp.1018-1030. ⟨10.1016/j.trecan.2020.07.006⟩ |
| ISSN: | 2405-8033 |
| DOI: | 10.1016/j.trecan.2020.07.006 |
| Popis: | International audience; IRE1α (inositol requiring enzyme 1 alpha) is one of the main transducers of the unfolded protein response (UPR). IRE1α plays instrumental protumoral roles in several cancers, and high IRE1α activity has been associated with poorer prognoses. In this context, IRE1α has been identified as a potentially relevant therapeutic target. Pharmacological inhibition of IRE1α activity can be achieved by targeting either the kinase domain or the RNase domain. Herein, the recent advances in IRE1α pharmacological targeting is summarized. We describe the identification and optimization of IRE1α inhibitors as well as their mode of action and limitations as anticancer drugs. The potential pitfalls and challenges that could be faced in the clinic, and the opportunities that IRE1α modulating strategies may present are discussed. |
| Databáze: | OpenAIRE |
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