ArticleCell death and differentiation2023
The anti-cancer agent APR-246 can activate several programmed cell death processes to kill malignant cells.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 36 citations in OpenAlex.
- Article
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- Wild-Type p53 Protein Enhances APR-246-Induced Cytotoxicity in Acute Myeloid Leukemia and Normal Hematopoietic Stem/Progenitor Cells.International journal of molecular sciences · 2026Article
- APR-246 drives ROS-dependent ferroptosis and apoptosis and enhances anti-PD-1 efficacy in bladder cancer.Scientific reports · 2026Article
- The MDM2-p53 Axis in Osteosarcoma: Current Understanding of Regulatory Mechanisms and Targeted Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Looking at the fraction with Annexin V⁺ and propidium iodide⁺: insights into cell death types from preclinical studies in solid and haematological cancers.Apoptosis : an international journal on programmed cell death · 2026Review
- Mutant p53 binds and controls estrogen receptor activity to drive endocrine resistance in ovarian cancer.Genes & development · 2026Article
- Functional restoration of conformational (R175H) and contact (R273H) mutant p53 byFrontiers in bioinformatics · 2026Article
- Non-small cell lung cancer after EGFR-TKI resistance: from drug resistance mechanisms to precision interventions.Frontiers in pharmacology · 2026Review
- Ferroptosis in hematological malignancies: molecular mechanisms and therapeutic potential.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Cell Death Disease turns 15: legacy of service, horizon of challenges.Cell death & disease · 2025Article
- A working group report from the 2024 National Cancer Institute / Gynecologic Cancer Steering Committee endometrial cancer clinical trials planning meeting: refining the approach to endometrial cancer in the immunotherapy era.Journal of the National Cancer Institute · 2025Article
- Genome-wide in vivo CRISPR screens identify GATOR1 complex as a tumor suppressor in Myc-driven lymphoma.Nature communications · 2025Article
- Small-Molecule Drugs in Pediatric Neuro-Oncology.Current oncology (Toronto, Ont.) · 2025Review
- Spanish consensus on the diagnosis and management of adrenocortical carcinoma.Endocrine-related cancer · 2025Review
- Review
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutant TP53 proteins are thought to drive the development and sustained expansion of cancers at least in part through the loss of the wild-type (wt) TP53 tumour suppressive functions. Therefore, compounds that can restore wt TP53 functions in mutant TP53 proteins are expected to inhibit the expansion of tumours expressing mutant TP53. APR-246 has been reported to exert such effects in malignant cells and is currently undergoing clinical trials in several cancer types. However, there is evidence that APR-246 may also kill malignant cells that do not express mutant TP53. To support the clinical development of APR-246 it is important to understand its mechanism(s) of action. By establishing isogenic background tumour cell lines with different TP53/TRP53 states, we found that APR-246 can kill malignant cells irrespective of their TP53/TRP53 status. Accordingly, RNAseq analysis revealed that treatment with APR-246 induces expression of the same gene set in Eμ-Myc mouse lymphoma cells of all four possible TRP53 states, wt, wt alongside mutant, knockout and knockout alongside mutant. We found that depending on the type of cancer cell and the concentration of APR-246 used, this compound can kill malignant cells through induction of various programmed cell death pathways, including apoptosis, necroptosis and ferroptosis. The sensitivity of non-transformed cells to APR-246 also depended on the cell type. These findings reveal that the clinical testing of APR-246 should not be limited to cancers expressing mutant TP53 but expanded to cancers that express wt TP53 or are TP53-deficient.
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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.