Detalle de: Cancer evolution and Peto’s paradox in primates

Cancer is primarily caused by specific mutations that accumulate in somatic cells over a lifetime. As individuals live longer or have more cells, their risk of developing cancer increases. Surprisingly, inter-species differences in longevity and size do not directly influence cancer prevalence—this phenomenon is known as Peto’s paradox. The mechanisms behind Peto’s paradox remain unclear, but the DNA damage response (DDR) plays a crucial role in controlling the accumulation of somatic mutations, and changes in DDR are widespread in species with low cancer prevalence. To investigate its role in Peto’s paradox, we study DDR across different cell types in humans and a panel of nonhuman primates with varying sizes and lifespans. We assess inter-species differences in cell-type-specific responses to mutagens using a combination of computational approaches, cell health assays, and genomic, epigenomic, and transcriptomic profiling. We aim to identify mutations and regulatory changes that control DNA damage and cancer prevalence in species closely related to humans, paving the way for new cancer and aging therapies.