Super-high tumor mutational burden predicts complete remission following immunotherapy: from Peto's paradox to druggable cancer hallmark.

ABSTRACT:

Background

The somatic mutation theory predicts that cancer risk should scale proportionally with lifetime cell divisions; yet large-bodied and long-lived species exhibit lower-than-expected cancer incidence-a long-standing contradiction termed Peto's paradox. Resolving this paradox and clarifying how tumor mutational burden (TMB) shapes treatment response to immune-checkpoint inhibitor (ICI) therapy remain unmet needs in precision oncology.

Methods

This study analyzed three data streams: (1) human cancer incidence data from North American registries; (2) cancer mortality records for 110,148 mammals (191 species) linked to body mass, life expectancy, and cancer risk, and (3) >30,000 tumors profiled in three independent pan-cancer cohorts and clinical outcomes in >2,700 ICI-t

SUBMITTER: Zheng M 

PROVIDER: S-EPMC12128474 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature