ArticleOncogene2022
p53 partial loss-of-function mutations sensitize to chemotherapy.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- Induction of differential cytotoxicity and ROS-driven severe genomic DNA damage and intrinsic mitochondrial apoptosis by erbium oxide nanoparticles in p53-compromised human NSCLC cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Co-treatment of Colchicine and Rosiglitazone synergistically inhibits cytokine-driven inflammation and modulates the related hsa-miRNA26a-5p, hsa-miRNA21-5p, and STAT3 expression in non-small cell lung cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Low-penetrance TP53 variants are mainly hypomorphic: an underestimated issue with high clinical significance.NPJ genomic medicine · 2026Article
- Engineering combination nanomedicines to overcome cancer resistance.RSC advances · 2026Review
- Ultra-deep duplex sequencing reveals unique features of somatic evolution in the normal tissues of a family with Li-Fraumeni syndrome.bioRxiv : the preprint server for biology · 2026Article
- TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a comprehensive overview of targeted approaches.Frontiers in oncology · 2026Review
- Insights into the olaparib-mediated cell death mechanisms in canine hematological malignancies: a different fate for CLBL-1 and GL-1 cell lines.Frontiers in veterinary science · 2026Article
- Pandora's Box of AML: HowBiomedicines · 2025Review
- Molecular Characteristics and Treatment Implications of TP53 Gain-of-Function Mutations in Non-Small Cell Lung Cancer.Cancer medicine · 2025Article
- The TP53 tumor suppressor gene: From molecular biology to clinical investigations.Journal of internal medicine · 2025Review
- Chromatin Immunoprecipitation Reveals p53 Binding to G-Quadruplex DNA Sequences in Myeloid Leukemia Cell Lines.ACS bio & med chem Au · 2025Article
- p53-deficient cancer cells hyperactivate DNA double-strand break repair pathways to overcome chemotherapeutic damage and augment survival.Molecular biology reports · 2025Article
- A line in shifting sand: Can we define and target TP53 mutated MDS?Seminars in hematology · 2024Review
- From regulation to deregulation of p53 in hematologic malignancies: implications for diagnosis, prognosis and therapy.Biomarker research · 2024Review
- Star wars against leukemia: attacking the clones.Leukemia · 2024Review
- TP53-mutated acute myeloid leukemia and myelodysplastic syndrome: biology, treatment challenges, and upcoming approaches.Annals of hematology · 2024Review
- ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework.NPJ precision oncology · 2024Review
- Article
- Pharmacological reactivation of p53 in the era of precision anticancer medicine.Nature reviews. Clinical oncology · 2024Review
- Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor suppressive transcription factor p53 is frequently inactivated in cancer cells by missense mutations that cluster in the DNA binding domain. 30% hit mutational hotspot residues, resulting in a complete loss of transcriptional activity and mutant p53-driven chemotherapy resistance. Of the remaining 70% of non-hotspot mutants, many are partial loss-of-function (partial-LOF) mutants with residual transcriptional activity. The therapeutic consequences of a partial-LOF have remained largely elusive. Using a p53 mutation engineered to reduce DNA binding, we demonstrate that partial-LOF is sufficient to enhance oncogene-driven tumorigenesis in mouse models of lung and pancreatic ductal adenocarcinoma and acute myeloid leukemia. Interestingly, mouse and human tumors with partial-LOF mutations showed mutant p53 protein accumulation similar as known for hotspot mutants. Different from the chemotherapy resistance caused by p53-loss, the partial-LOF mutant sensitized to an apoptotic chemotherapy response and led to a survival benefit. Mechanistically, the pro-apoptotic transcriptional activity of mouse and human partial-LOF mutants was rescued at high mutant protein levels, suggesting that accumulation of partial-LOF mutants enables the observed apoptotic chemotherapy response. p53 non-hotspot mutants with partial-LOF, therefore, represent tumorigenic p53 mutations that need to be distinguished from other mutations because of their beneficial impact on survival in a therapy context.
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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.