A disease model resource reveals core principles of tissue-specific cancer evolution

Nature

by Sebastian Mueller

February 26, 2026

AI-Generated Deep Dive Summary

A groundbreaking study highlights the importance of tissue-specific cancer evolution by examining how oncogenes like KRAS behave differently across various tissues. Researchers developed the Mouse Cancer Cell line Atlas (MCCA), a comprehensive resource comprising 590 meticulously characterized mouse cancer cell lines spanning 22 cell lineages and 46 disease types. This innovative tool enables scientists to study cancer progression in diverse tissue contexts, revealing key principles that dictate how cancers evolve differently depending on their location in the body. The MCCA reveals that mutant KRAS exerts its oncogenic effects in a cell-type-specific manner. For instance, in pancreatic cancer, higher doses of mutant KRAS trigger dosage-sensitive developmental reprogramming, which influences disease progression. Similarly, tissue- and stage-specific evolutionary requirements—such as blocking differentiation in intestinal tissues—shape how KRAS collaborates with other genetic alterations. These findings underscore the importance of understanding how oncogenes interact with their specific cellular environments. By analyzing these interactions, researchers identified context-dependent epistatic relationships between KRAS and tumor suppressors, which determine the patterns and timing of cancer gene alterations. This deterministic model of cancer evolution explains why certain genomic changes are more prevalent in particular tissues. For example, reciprocal dosage sensitivities dictate how frequently and at what stage specific alterations arise during cancer development. The study’s significance lies in its ability to predict molecular patterns and temporal dynamics of cancer evolution across tissues. These insights are critical for advancing personalized medicine, as they highlight the need to tailor cancer treatments based on tissue-specific genetic and evolutionary contexts. The MCCA serves as a powerful tool for researchers to explore these mechanisms further, ultimately paving the way for more effective therapeutic strategies.

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Originally published on Nature on 2/26/2026