ArticleEMBO molecular medicine2021
A thiol-bound drug reservoir enhances APR-246-induced mutant p53 tumor cell death.
Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Revisiting tumor immunogenicity through the lens of mutant p53: Implications for cancer immunotherapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Unbiased assessment of APR-246 responsive p53 mutants in ovarian cancer.Cell death discovery · 2026Article
- Chronic and non-canonical cGAS-STING activation: implications for health, disease, cancer, and emerging therapeutic opportunities.Apoptosis : an international journal on programmed cell death · 2026Review
- The impact of p53 mutation on tumor immune evasion: mechanistic insights and clinical implications.Frontiers in immunology · 2026Review
- PK11007 Covalently Inhibits Thioredoxin Reductase 1 to Induce Oxidative Stress and Autophagy Impairment in NSCLC Cells.Antioxidants (Basel, Switzerland) · 2025Article
- DNA methylation and transcription factor-driven immune subtypes in ovarian cancer.Discover oncology · 2025Article
- APR-246 as a radiosensitization strategy for mutant p53 cancers treated with alpha-particles-based radiotherapy.Cell death & disease · 2024Article
- p53 biology and reactivation for improved therapy in MDS and AML.Biomarker research · 2024Review
- Translating p53-based therapies for cancer into the clinic.Nature reviews. Cancer · 2024Review
- Caspase-2 protects against ferroptotic cell death.Cell death & disease · 2024Article
- Pharmacological reactivation of p53 in the era of precision anticancer medicine.Nature reviews. Clinical oncology · 2024Review
- Neuroblastoma response to RAS-MAPK inhibitors and APR-246 (eprenetapopt) co-treatment is dependent on SLC7A11.Frontiers in oncology · 2024Article
- PTC596-Induced BMI-1 Inhibition Fights Neuroblastoma Multidrug Resistance by Inducing Ferroptosis.Antioxidants (Basel, Switzerland) · 2023Article
- Deep learning untangles the resistance mechanism of p53 reactivator in lung cancer cells.iScience · 2023Article
- APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy.Molecular cancer therapeutics · 2023Article
- Small-molecule correctors and stabilizers to target p53.Trends in pharmacological sciences · 2023Review
- Eprenetapopt triggers ferroptosis, inhibits NFS1 cysteine desulfurase, and synergizes with serine and glycine dietary restriction.Science advances · 2022Article
- Alternative Lengthening of Telomeres in Cancer Confers a Vulnerability to Reactivation of p53 Function.Cancer research · 2022Article
- Targeting MDM4 as a Novel Therapeutic Approach in Prostate Cancer Independent of p53 Status.Cancers · 2022Article
- Li-Fraumeni Syndrome: Mutation ofCancers · 2022Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
The tumor suppressor gene TP53 is the most frequently mutated gene in cancer. The compound APR-246 (PRIMA-1Met/Eprenetapopt) is converted to methylene quinuclidinone (MQ) that targets mutant p53 protein and perturbs cellular antioxidant balance. APR-246 is currently tested in a phase III clinical trial in myelodysplastic syndrome (MDS). By in vitro, ex vivo, and in vivo models, we show that combined treatment with APR-246 and inhibitors of efflux pump MRP1/ABCC1 results in synergistic tumor cell death, which is more pronounced in TP53 mutant cells. This is associated with altered cellular thiol status and increased intracellular glutathione-conjugated MQ (GS-MQ). Due to the reversibility of MQ conjugation, GS-MQ forms an intracellular drug reservoir that increases availability of MQ for targeting mutant p53. Our study shows that redox homeostasis is a critical determinant of the response to mutant p53-targeted cancer therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.