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Epigenetic Heritability of Cell Plasticity Drives Cancer Drug Resistance through a One-to-Many Genotype-to-Phenotype Paradigm.

Cancer research - 1 Aug 2025

Oliveira Erica A, Milite Salvatore, Fernandez-Mateos Javier, Cresswell George D, Yara-Romero Erika, Vlachogiannis Georgios, Chen Bingjie, James Chela T, Patruno Lucrezia, Ascolani Gianluca, Acar Ahmet, Heide Timon, Spiteri Inmaculada, Graudenzi Alex, Caravagna Giulio, Bertotti Andrea, Graham Trevor A, Magnani Luca, Valeri Nicola, Sottoriva Andrea

Abstract excerpt

Cancer drug resistance is multifactorial, driven by heritable (epi)genetic changes but also by phenotypic plasticity. In this study, we dissected the drivers of resistance by perturbing organoids derived from patients with colorectal cancer longitudinally with drugs in sequence. Combined longitudinal lineage tracking, single-cell multiomics analysis, evolutionary modeling, and machine learning revealed that...

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Cell Plasticity
Clonal Evolution
Colorectal Neoplasms
Drug Resistance, Neoplasm

Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Epigenesis, Genetic

Gene Expression Regulation, Neoplastic

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Identifiers

PMID: 40499006
DOI: 10.1158/0008-5472.CAN-25-0999
PMCID: PMC12314525

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