mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node
Abstract Mechanistic target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that regulates key cellular processes including cell growth, autophagy and metabolism. Hyperactivation of the mTOR pathway causes a group of rare and ultrarare genetic diseases. mTOR pathway diseases have d...
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| Format: | Article |
| Language: | English |
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2025-05-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03740-1 |
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| author | Laura Mantoan Ritter Nicholas M. P. Annear Emma L. Baple Leila Y. Ben-Chaabane Istvan Bodi Lauren Brosson Jill E. Cadwgan Bryn Coslett Andrew H. Crosby D. Mark Davies Nicola Daykin Stefanie Dedeurwaerdere Christina Dühring Fenger Elaine A. Dunlop Frances V. Elmslie Marie Girodengo Sophie Hambleton Anna C. Jansen Simon R. Johnson Kelly C. Kearley John C. Kingswood Liisi Laaniste Katherine Lachlan Andrew Latchford Ralitsa R. Madsen Sahar Mansour Simeon R. Mihaylov Louwai Muhammed Claire Oliver Tom Pepper Lettie E. Rawlins Ina Schim van der Loeff Ata Siddiqui Pooja Takhar Katrina Tatton-Brown Andrew R. Tee Priyanka Tibarewal Charlotte Tye Sila K. Ultanir Bart Vanhaesebroeck Benjamin Zare Deb K. Pal Joseph M. Bateman |
| author_facet | Laura Mantoan Ritter Nicholas M. P. Annear Emma L. Baple Leila Y. Ben-Chaabane Istvan Bodi Lauren Brosson Jill E. Cadwgan Bryn Coslett Andrew H. Crosby D. Mark Davies Nicola Daykin Stefanie Dedeurwaerdere Christina Dühring Fenger Elaine A. Dunlop Frances V. Elmslie Marie Girodengo Sophie Hambleton Anna C. Jansen Simon R. Johnson Kelly C. Kearley John C. Kingswood Liisi Laaniste Katherine Lachlan Andrew Latchford Ralitsa R. Madsen Sahar Mansour Simeon R. Mihaylov Louwai Muhammed Claire Oliver Tom Pepper Lettie E. Rawlins Ina Schim van der Loeff Ata Siddiqui Pooja Takhar Katrina Tatton-Brown Andrew R. Tee Priyanka Tibarewal Charlotte Tye Sila K. Ultanir Bart Vanhaesebroeck Benjamin Zare Deb K. Pal Joseph M. Bateman |
| author_sort | Laura Mantoan Ritter |
| collection | DOAJ |
| description | Abstract Mechanistic target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that regulates key cellular processes including cell growth, autophagy and metabolism. Hyperactivation of the mTOR pathway causes a group of rare and ultrarare genetic diseases. mTOR pathway diseases have diverse clinical manifestations that are managed by distinct medical disciplines but share a common underlying molecular basis. There is a now a deep understanding of the molecular underpinning that regulates the mTOR pathway but effective treatments for most mTOR pathway diseases are lacking. Translating scientific knowledge into clinical applications to benefit the unmet clinical needs of patients is a major challenge common to many rare diseases. In this article we expound how mTOR pathway diseases provide an opportunity to coordinate basic and translational disease research across the group, together with industry, medical research foundations, charities and patient groups, by pooling expertise and driving progress to benefit patients. We outline the germline and somatic mutations in the mTOR pathway that cause rare diseases and summarise the prevalence, genetic basis, clinical manifestations, pathophysiology and current treatments for each disease in this group. We describe the challenges and opportunities for progress in elucidating the underlying mechanisms, improving diagnosis and prognosis, as well as the development and approval of new therapies for mTOR pathway diseases. We illustrate the crucial role of patient public involvement and engagement in rare disease and mTOR pathway disease research. Finally, we explain how the mTOR Pathway Diseases node, part of the Research Disease Research UK Platform, will address these challenges to improve the understanding, diagnosis and treatment of mTOR pathway diseases. |
| format | Article |
| id | doaj-art-a476cadf17cc442fa68e6dbdb9e81570 |
| institution | OA Journals |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-a476cadf17cc442fa68e6dbdb9e815702025-08-20T02:00:08ZengBMCOrphanet Journal of Rare Diseases1750-11722025-05-0120113310.1186/s13023-025-03740-1mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR nodeLaura Mantoan Ritter0Nicholas M. P. Annear1Emma L. Baple2Leila Y. Ben-Chaabane3Istvan Bodi4Lauren Brosson5Jill E. Cadwgan6Bryn Coslett7Andrew H. Crosby8D. Mark Davies9Nicola Daykin10Stefanie Dedeurwaerdere11Christina Dühring Fenger12Elaine A. Dunlop13Frances V. Elmslie14Marie Girodengo15Sophie Hambleton16Anna C. Jansen17Simon R. Johnson18Kelly C. Kearley19John C. Kingswood20Liisi Laaniste21Katherine Lachlan22Andrew Latchford23Ralitsa R. Madsen24Sahar Mansour25Simeon R. Mihaylov26Louwai Muhammed27Claire Oliver28Tom Pepper29Lettie E. Rawlins30Ina Schim van der Loeff31Ata Siddiqui32Pooja Takhar33Katrina Tatton-Brown34Andrew R. Tee35Priyanka Tibarewal36Charlotte Tye37Sila K. Ultanir38Bart Vanhaesebroeck39Benjamin Zare40Deb K. Pal41Joseph M. Bateman42King’s College London Institute of Psychiatry Psychology and NeuroscienceSt George’s University Hospitals NHS Foundation TrustUniversity of Exeter Medical SchoolKing’s College London Institute of Psychiatry Psychology and NeuroscienceKing’s College Hospital NHS Foundation TrustmTOR Node Advisory Panel (MAP)Guy’s and St Thomas’s NHS Foundation TrustmTOR Node Advisory Panel (MAP)University of Exeter Medical SchoolCardiff UniversitymTOR Node Advisory Panel (MAP)UCB Biopharma SRLAmplexa GeneticsCardiff UniversitySt George’s University Hospitals NHS Foundation TrustKing’s College London Institute of Psychiatry Psychology and NeuroscienceNewcastle University Translational and Clinical Research Institute, Newcastle UniversityAntwerp University HospitalCentre for Respiratory Research, NIHR Nottingham Biomedical Research Centre and Biodiscovery Institute, Translational Medical Sciences, University of NottinghammTOR Node Advisory Panel (MAP)St George’s University Hospitals NHS Foundation TrustCoSyne TherapeuticsUniversity Hospital Southampton NHS Foundation TrustPolyposis Registry, St Mark’s HospitalUniversity of Dundee School of Life SciencesSt George’s University Hospitals NHS Foundation TrustThe Francis Crick InstituteCoSyne TherapeuticsmTOR Node Advisory Panel (MAP)PTEN ResearchUniversity of Exeter Medical SchoolNewcastle University Translational and Clinical Research Institute, Newcastle UniversityKing’s College Hospital NHS Foundation TrustTuberous Sclerosis AssociationSt George’s University Hospitals NHS Foundation TrustCardiff UniversityUCL Cancer InstituteKing’s College London Institute of Psychiatry Psychology and NeuroscienceThe Francis Crick InstituteUCL Cancer InstitutePolyposis Registry, St Mark’s HospitalKing’s College London Institute of Psychiatry Psychology and NeuroscienceKing’s College London Institute of Psychiatry Psychology and NeuroscienceAbstract Mechanistic target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that regulates key cellular processes including cell growth, autophagy and metabolism. Hyperactivation of the mTOR pathway causes a group of rare and ultrarare genetic diseases. mTOR pathway diseases have diverse clinical manifestations that are managed by distinct medical disciplines but share a common underlying molecular basis. There is a now a deep understanding of the molecular underpinning that regulates the mTOR pathway but effective treatments for most mTOR pathway diseases are lacking. Translating scientific knowledge into clinical applications to benefit the unmet clinical needs of patients is a major challenge common to many rare diseases. In this article we expound how mTOR pathway diseases provide an opportunity to coordinate basic and translational disease research across the group, together with industry, medical research foundations, charities and patient groups, by pooling expertise and driving progress to benefit patients. We outline the germline and somatic mutations in the mTOR pathway that cause rare diseases and summarise the prevalence, genetic basis, clinical manifestations, pathophysiology and current treatments for each disease in this group. We describe the challenges and opportunities for progress in elucidating the underlying mechanisms, improving diagnosis and prognosis, as well as the development and approval of new therapies for mTOR pathway diseases. We illustrate the crucial role of patient public involvement and engagement in rare disease and mTOR pathway disease research. Finally, we explain how the mTOR Pathway Diseases node, part of the Research Disease Research UK Platform, will address these challenges to improve the understanding, diagnosis and treatment of mTOR pathway diseases.https://doi.org/10.1186/s13023-025-03740-1mTORRare diseasesTuberous sclerosis complexPTENPI3KAKT |
| spellingShingle | Laura Mantoan Ritter Nicholas M. P. Annear Emma L. Baple Leila Y. Ben-Chaabane Istvan Bodi Lauren Brosson Jill E. Cadwgan Bryn Coslett Andrew H. Crosby D. Mark Davies Nicola Daykin Stefanie Dedeurwaerdere Christina Dühring Fenger Elaine A. Dunlop Frances V. Elmslie Marie Girodengo Sophie Hambleton Anna C. Jansen Simon R. Johnson Kelly C. Kearley John C. Kingswood Liisi Laaniste Katherine Lachlan Andrew Latchford Ralitsa R. Madsen Sahar Mansour Simeon R. Mihaylov Louwai Muhammed Claire Oliver Tom Pepper Lettie E. Rawlins Ina Schim van der Loeff Ata Siddiqui Pooja Takhar Katrina Tatton-Brown Andrew R. Tee Priyanka Tibarewal Charlotte Tye Sila K. Ultanir Bart Vanhaesebroeck Benjamin Zare Deb K. Pal Joseph M. Bateman mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node Orphanet Journal of Rare Diseases mTOR Rare diseases Tuberous sclerosis complex PTEN PI3K AKT |
| title | mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node |
| title_full | mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node |
| title_fullStr | mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node |
| title_full_unstemmed | mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node |
| title_short | mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node |
| title_sort | mtor pathway diseases challenges and opportunities from bench to bedside and the mtor node |
| topic | mTOR Rare diseases Tuberous sclerosis complex PTEN PI3K AKT |
| url | https://doi.org/10.1186/s13023-025-03740-1 |
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