ArticleCell death discovery2026
Unbiased assessment of APR-246 responsive p53 mutants in ovarian cancer.
Article in Cell death discovery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
TP53 is the most frequently mutated gene in high-grade serous ovarian cancer, and the majority of these mutations result in overexpression of mutant p53. Therefore, therapies that can restore the wild-type activities from p53 mutants have the potential to cause p53-mediated tumor suppressive effects. Accordingly, prior studies have shown that APR-246 can bind to specific p53 mutants, restore wild-type activities, and cause tumor suppression in cancer cell lines with hot-spot mutations. However, systematic analysis of what other p53 mutants are responsive to APR-246 is currently lacking. Here, we used a TP53 mutagenesis library to perform functional genetic screens to identify TP53 mutants that are sensitive to APR-246. Our studies confirm weak p53-dependent cytotoxic/cytostatic effects in OVCAR5 but not in SKOV3 and CAOV3. Further analysis identified ferroptosis sensitivity as a major determinant of APR-246 sensitivity. This agrees with the known effect of APR-246 as a disruptor of the redox system. In ferroptosis-sensitive SKOV3 and CAOV3, p53-dependent effects are not observable because APR-246 acts primarily through its induction of ferroptosis. Only in OVCAR5, which is relatively insensitive to ferroptosis compared to SKOV3 and CAOV3, do we observe a p53-dependent effect of APR-246. This study demonstrates that p53-specific effects of APR-246 are only observable in a narrow dosing window, under a specific set of conditions. Collectively, our results highlight the limitation of APR-246 as a p53-rescuing drug because of its overwhelming off-target effects on the redox system at doses that are sufficient to induce ferroptosis but insufficient to rescue mutant p53.
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Registered trials
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