Study uncovers mutations in tp53 driving resistance to rezatapopt treatment, suggesting challenges in cancer therapies.
The study by Fece de la Cruz, Varkaris, and colleagues uncovered a critical mechanism underlying resistance to the p53-Y220C reactivator rezatapopt in the PYNNACLE clinical trial. Specifically, rezatapopt treatment was shown to select for secondary mutations in the TP53 gene on the Y220C-mutant background, thereby abrogating its therapeutic efficacy. See related article by Fece de la Cruz et al., p. 677.
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