Moving beyond the neutral-Darwinian dichotomy to inform precision oncology.

Abstract

Current methods for distinguishing neutral from selection-driven tumour evolution rely on assumptions frequently violated in clinical samples. We argue that tumour evolution is not a binary state, but a dynamic continuum shaped by genetic and non-genetic heterogeneity, spatial constraints, microenvironmental pressures and therapeutic bottlenecks. Refining evolutionary inference through integrative, longitudinal and spatially resolved analyses will be essential to align these models with therapeutic decision-making in precision oncology.