332-Cell State Plasticity Drives Olaparib Resistance
The paper introduces the concept of the "resistance continuum," a framework explaining how cancer cells gradually adapt to therapy through a dynamic series of cell-state transitions, rather than just immediate genetic mutations. Through longitudinal dose-escalation experiments in various cancer cell lines, researchers demonstrate that resistance is progressively acquired and accompanied by increasing cell fitness. This adaptation involves non-genetic plasticity, including epithelial-to-mesenchymal transition (EMT) as an enabling factor, and the stepwise assembly of new gene expression…
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