Universal scaling laws rule explosive growth in human cancers
Victor Pérez-García
(1)
,
Gabriel F Calvo
(1)
,
Jesús J Bosque
(1)
,
Odelaisy León-Triana
(1)
,
Juan Jiménez
(1)
,
Julián Pérez-Beteta
(1)
,
Juan Belmonte-Beitia
(1)
,
Manuel Valiente
(2)
,
Lucía Zhu
(2)
,
Pedro García-Gómez
(2)
,
Pilar Sánchez-Gómez
(3)
,
Esther Hernández-San Miguel
(3)
,
Rafael Hortigüela
(3)
,
Youness Azimzade
(4)
,
David Molina-García
(1)
,
Álvaro Martínez
(1)
,
Ángel Acosta Rojas
(5)
,
Ana Ortiz de Mendivil
(5)
,
François M. Vallette
(6)
,
Philippe Schucht
(7)
,
Michael Murek
(7)
,
María Pérez-Cano
(1)
,
David Albillo
(8)
,
Antonio F Honguero Martínez
(9)
,
Germán A Jiménez Londoño
(10)
,
Estanislao Arana
(11)
,
Ana García Vicente
(10)
1
UCLM -
Universidad de Castilla-La Mancha = University of Castilla-La Mancha
2 CNIO - Spanish National Cancer Research Center
3 Institute of Health Carlos III
4 University of Tehran
5 Sanchinarro University Hospita [HM Hospitales, Madrid]
6 CRCINA-ÉQUIPE 9 - Apoptosis and Tumor Progression
7 Inselspital - Bern University Hospital [Berne]
8 MD Anderson Cancer Center [Madrid, Spain]
9 Hospital General Universitario de Albacete
10 HGUCR - Hospital General Universitario de Ciudad Real [Ciudad Real, Spain]
11 Fundación Instituto Valenciano de Oncología [Valencia, Spain]
2 CNIO - Spanish National Cancer Research Center
3 Institute of Health Carlos III
4 University of Tehran
5 Sanchinarro University Hospita [HM Hospitales, Madrid]
6 CRCINA-ÉQUIPE 9 - Apoptosis and Tumor Progression
7 Inselspital - Bern University Hospital [Berne]
8 MD Anderson Cancer Center [Madrid, Spain]
9 Hospital General Universitario de Albacete
10 HGUCR - Hospital General Universitario de Ciudad Real [Ciudad Real, Spain]
11 Fundación Instituto Valenciano de Oncología [Valencia, Spain]
Résumé
Most physical and other natural systems are complex entities that are composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws that relate an observable quantity to 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, owing to evolutionary dynamics, that leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of patients with cancer. To explain our observations we tested complex, biologically inspired mathematical models that describe the key processes that govern tumour growth. Our models predict that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws that we identified allowed us to define a set of metabolic metrics with prognostic value, which adds clinical utility to our findings.