Universal scaling laws rule explosive growth in human cancers [Pre-print]
| Autor: | Pérez-García, Víctor M, Calvo, Gabriel F, Bosque, Jesús J, León-Triana, Odelaisy, Jiménez, Juan, Perez-Beteta, Julián, Belmonte-Beitia, Juan, Zhu, Lucía, García-Gómez, Pedro, Sanchez-Gomez, Pilar, Hernandez-Sanmiguel, Esther, Hortigüela, Rafael, Azimzade, Youness, Molina-García, David, Martinez, Álvaro, Rojas, Ángel Acosta, de Mendivil, Ana Ortiz, Vallette, Francois, Schucht, Philippe, Murek, Michael, Pérez-Cano, María, Albillo, David, Honguero Martínez, Antonio F, Jiménez Londoño, Germán A, Arana, Estanislao, García Vicente, Ana M, Valiente, Manuel |
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| Přispěvatelé: | James S. McDonnell Foundation, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Regional Government of Castile-La Mancha (España), Ministerio de Economía y Competitividad (España), Bristol-Myers Squibb, Beug Foundation for Metastasis Research, Fundación Ramón Areces, Worldwide Cancer Research, Unión Europea. Comisión Europea. H2020, Fundación La Marató TV3, Clinic and Laboratory Integration Program CRI Award 2018, Asociación Española Contra el Cáncer, Fundación La Caixa, Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España), European Molecular Biology Organization |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Repisalud Instituto de Salud Carlos III (ISCIII) |
| Popis: | Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws relating an observable quantity with a measure of the size of the system. Here we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, due to evolutionary dynamics, which leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of cancer patients. To explain our observations we put forward increasingly-complex biologically-inspired mathematical models that captured the key processes governing tumor growth. Our models predicted that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws thereby identified allowed us to define a set of metabolic metrics with prognostic value, thus providing added clinical utility to the base findings. This research has been supported by the James S. McDonnell Foundation 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer (collaborative awards 220020560 and 220020450), Ministerio de Economia y Competitividad/FEDER, Spain (grant no. MTM2015-71200-R), Junta de Comunidades de Castilla-La Mancha (grant no. SBPLY/17/180501/000154). Research in the Brain Metastasis Group is supported by MINECO grant MINECO-Retos SAF2017-89643-R (M.V.), Bristol-Myers Squibb Melanoma Research Alliance Young Investigator Award 2017 (498103) (M.V.), Beug Foundation's Prize for Metastasis Research 2017 (M.V.), Fundacion Ramon Areces (CIVP19S8163) (M.V.), Worldwide Cancer Research (19-0177) (M.V.), H2020-FETOPEN (828972) (M.V.), Fundacio La Marato de tv3 (141), Clinic and Laboratory Integration Program CRI Award 2018 (54545) (M.V.), AECC Coordinated Translational Groups 2017 (GCTRA16015SEOA) (M.V.), LAB AECC 2019 (LABAE19002VALI) (M.V.), La Caixa INPhINIT Fellowship (LCF/BQ/IN17/11620028) (P.G.-G.), La Caixa-Severo Ochoa International PhD Program Fellowship (LCF/BQ/SO16/52270014) (L.Z.). M.V. is a member of the European Molecular Biology Organization Young Investigators programme (4053). We would like to acknowledge J. Cervera and J. C. Penalver from the IVO Foundation (Valencia, Spain). No |
| Databáze: | OpenAIRE |
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