Clear cell renal cell carcinoma (CCRCC) is an aggressive form of cancer and a paradigmatic example of intratumor heterogeneity (ITH). The hawk-dove game is a mathematical tool designed to analyze competition in biological systems. Using this game, the study reported here analyzes the early phase of CCRCC development, comparing clonal fitness in homogeneous (linear evolutionary) and highly heterogeneous (branching evolutionary) models. Fitness in the analysis is a measure of tumor aggressiveness. The results show that the fittest clone in a heterogeneous environment is fitter than the clone in a homogeneous context in the early phases of tumor evolution. Early and late periods of tumor evolution in CCRCC are also compared. The study shows the convergence of mathematical, histological, and genomics studies with respect to clonal aggressiveness in different periods of the natural history of CCRCC. Such convergence highlights the importance of multidisciplinary approaches for obtaining a better understanding of the intricacies of cancer.
Cancers. 2023 Dec 18*** epublish ***
Annick Laruelle, Claudia Manini, José I López, André Rocha
Department of Economic Analysis, University of the Basque Country (UPV/EHU), 48015 Bilbao, Spain., Department of Pathology, San Giovanni Bosco Hospital, ASL Città di Torino, 10154 Turin, Italy., Biomarkers in Cancer, Biocruces-Bizkaia Health Research Institute, 48903 Barakaldo, Spain., Department of Industrial Engineering, Pontifical Catholic University of Rio de Janeiro, Rio de Janeiro CEP22451-900, Brazil.