ArticleCancer letters2024
Patient-derived tumor organoids with p53 mutations, and not wild-type p53, are sensitive to synergistic combination PARP inhibitor treatment.
Article in Cancer letters, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Construction and application of mammary and breast cancer organoids.Cell insight · 2026Review
- 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
- Patient-derived organoids across cancers reveal conserved tumor heterogeneity and actionable therapeutic vulnerabilities.Science advances · 2026Article
- Fuzuloparib enhances radiosensitivity of gain-of-function mutant p53 R273H NSCLC by promoting SLC7A11/GSH/GPX4 axis mediated ferroptosis.NPJ precision oncology · 2026Article
- Mutant p53 Directs PARP to Regulate Replication Stress and Drive Breast Cancer Metastasis.bioRxiv : the preprint server for biology · 2026Article
- Patient-Derived Organoids as a Platform to Decipher and Overcome Radioresistance: From the Tumor Microenvironment to Radiosensitizer Discovery.Current oncology (Toronto, Ont.) · 2025Review
- A cancer persistent DNA repair circuit driven by MDM2, MDM4 (MDMX), and mutant p53 for recruitment of MDC1 and 53BP1 on chromatin.Nucleic acids research · 2025Article
- Cholesterol inhibition enhances antitumor response of gilteritinib in lung cancer cells.Cell death & disease · 2024Article
- A comprehensive molecular characterization of a claudin-low luminal B breast tumor.Biology direct · 2024Article
- The Transformative Role of 3D Culture Models in Triple-Negative Breast Cancer Research.Cancers · 2024Review
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Authors and funding
26 authors at 7 institutions in 3 countries.
Funding
Abstract
Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with BRCA1/2 mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than BRCA1/2 is mutation to the TP53 gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein. Combination drug treatment with the alkylating agent temozolomide and the PARPi talazoparib kills mtp53 expressing 2D grown breast cancer cell lines. We evaluated the sensitivity to the combination of temozolomide plus PARPi talazoparib treatment to breast and lung cancer patient-derived tumor organoids (PDTOs). The combination of the two drugs was synergistic for a cytotoxic response in PDTOs with mtp53 but not for PDTOs with wtp53. The combination of talazoparib and temozolomide induced more DNA double-strand breaks in mtp53 expressing organoids than in wild-type p53 expressing organoids as shown by increased γ-H2AX protein expression. Moreover, breast cancer tissue microarrays (TMAs) showed a positive correlation between stable p53 and high PARP1 expression in sub-groups of breast cancers, which may indicate sub-classes of breast cancers sensitive to PARPi therapy. These results suggest that mtp53 could be a biomarker to predict response to the combination of PARPi talazoparib-temozolomide treatment.
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