Cancer evolution: from Darwin to the Extended Evolutionary Synthesis

The fundamental evolutionary nature of cancer has been recognized for decades. Increasingly powerful genetic and single cell sequencing technologies, as well as preclinical models, continue to unravel the evolution of premalignant cells, and progression to metastatic stages and to drug-resistant end-stage disease. Here, we summarize recent advances and distil evolutionary principles and their relevance for the clinic. We reveal how cancer cell and microenvironmental plasticity are intertwined with Darwinian evolution and demonstrate the need for a conceptual framework that integrates these processes. This warrants the adoption of the recently developed Extended Evolutionary Synthesis (EES).