Abstract IA018: The evolutionary origins of cancer lethality

Abstract Cancer is fundamentally a disease of evolution. But why do some cancers evolve into lethal entities while others rarely if ever evolve the capacity to metastasize and become lethal? We will explore how each of the cancer genome, transcriptome, proteome, gene-regulation and microenvironment are dysregulated in ways that explain variable clinical outcomes. Taken together, these converge on an evolutionary understanding of when the capacity to become lethal emerges, and how to predict that. We will conclude by briefly discussing the underlying genetic and lifestyle factors that influence the emergence of lethality, and that may give some indications of improved prevention and mitigation strategies. Citation Format: Paul C Boutros. The evolutionary origins of cancer lethality [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr IA018.