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Highlights • Periods of chromosomal instability can accelerate acquisition of drug resistance • Drug-resistant cancer cells frequently harbor recurrent aneuploidies • Recapitulation of an aneuploidy in drug-naive cells is sufficient for resistance • Chromosomal instability correlates with poor therapeutic responses in human tumors Summary Aneuploidy is a ubiquitous feature of human tumors, but the acquisition of aneuploidy typically antagonizes cellular fitness.
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