Divergent evolutionary dynamics of benign and malignant tumors

G George Butler (University College London Cancer Institute, University College London) J Joanna Baker (School of Biological Science, University of Reading) S Sarah R. Amend (Urology and Oncology Cancer Ecology Center at the Brady Urological Institute Johns Hopkins School of Medicine Baltimore Maryland USA) K Kenneth J. Pienta (Urology, Oncology, Pharmacology and Molecular Sciences, and Chemical and Biomolecular Engineering Cancer Ecology Center at the Brady Urological Institute Johns Hopkins University Baltimore Maryland USA) C Chris Venditti (School of Biological Science, University of Reading)

Abstract

Benign and malignant (cancerous) tumors differ markedly in their impact on organismal fitness, yet studies in comparative oncology rarely distinguish between them. Using a Bayesian phylogenetic framework across birds and mammals, we show that while both tumor types increase in prevalence with body mass, only the prevalence of malignant tumors is negatively associated with the rate of body size evolution—suggesting that adaptive mechanisms of cancer defense are associated with rapidly evolving lineages. Additionally, the rate of lineage diversification is positively associated with the prevalence of both tumor types in birds but not mammals, potentially reflecting differences in genome architecture and speciation dynamics. Together, these results highlight distinct macroevolutionary drivers of benign versus malignant tumor prevalence and underscore the value of treating tumor types separately in comparative oncology.

Article Details

Volume / Issue Vol. 122, Issue 45
Published November 11, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (5)

G

George Butler

University College London Cancer Institute, University College London

J

Joanna Baker

School of Biological Science, University of Reading

S

Sarah R. Amend

Urology and Oncology Cancer Ecology Center at the Brady Urological Institute Johns Hopkins School of Medicine Baltimore Maryland USA

K

Kenneth J. Pienta

Urology, Oncology, Pharmacology and Molecular Sciences, and Chemical and Biomolecular Engineering Cancer Ecology Center at the Brady Urological Institute Johns Hopkins University Baltimore Maryland USA

C

Chris Venditti

School of Biological Science, University of Reading