ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
KAT6A Condensates Impair PARP1 Trapping of PARP Inhibitors in Ovarian Cancer.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Nanotherapeutics for enhanced treatments for ovarian cancer: a comprehensive minireview.Drug delivery · 2026Review
- Article
- Lysine Acetyltransferase 6A Drives M1 Macrophage Polarization Through Metabolic Reprogramming in Sepsis-Induced Acute Lung Injury.Biomolecules · 2026Article
- Liquid-liquid phase separation in cancer therapy resistance.iScience · 2026Review
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- Cellular strategies for repairing trapped protein-DNA complexes.Frontiers in pharmacology · 2026Review
- Overcoming Resistance to PARP Inhibitors in BRCA-Mutated Cancers: Mechanisms and Therapeutic Strategies.Journal of Cancer · 2026Review
- Mechanisms of resistance to PARP inhibitors in advanced epithelial ovarian cancer: biological determinants and therapeutic implications.Frontiers in oncology · 2026Review
- PARPs and PARP inhibitors: molecular mechanisms and clinical applications.Molecular biomedicine · 2025Review
- Lysine Acetyltransferase 6 in Health and Disease.MedComm · 2025Review
- Navigating PARP Inhibitor Resistance in Ovarian Cancer: Bridging Mechanistic Insights To Clinical Translation.Current treatment options in oncology · 2025Review
- Biomolecular phase separation in tumorigenesis: from aberrant condensates to therapeutic vulnerabilities.Molecular cancer · 2025Review
- The Trim32-DPEP2 axis is an inflammatory switch in macrophages during intestinal inflammation.Cell death and differentiation · 2025Article
- CircDNA2-Educated YTHDF2 Phase Separation Promotes PMAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- SLC40A1-mediated positive feedback loop with M1 macrophages suppresses epithelial ovarian cancer progression.Frontiers in immunology · 2025Article
- KAT6A Condensates Impair PARP1 Trapping of PARP Inhibitors in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
6 authors.
Funding
Abstract
Most clinical PARP inhibitors (PARPis) trap PARP1 in a chromatin-bound state, leading to PARPi-mediated cytotoxicity. PARPi resistance impedes the treatment of ovarian cancer in clinical practice. However, the mechanism by which cancer cells overcome PARP1 trapping to develop PARPi resistance remains unclear. Here, it is shown that high levels of KAT6A promote PARPi resistance in ovarian cancer, regardless of its catalytic activity. Mechanistically, the liquid-liquid phase separation (LLPS) of KAT6A, facilitated by APEX1, inhibits the cytotoxic effects of PARP1 trapping during PARPi treatment. The stable KAT6A-PARP1-APEX1 complex reduces the amount of PARP1 trapped at the DNA break sites. In addition, inhibition of KAT6A LLPS, rather than its catalytic activity, impairs DNA damage repair and restores PARPi sensitivity in ovarian cancer both in vivo and in vitro. In conclusion, the findings demonstrate the role of KAT6A LLPS in fostering PARPi resistance and suggest that repressing KAT6A LLPS can be a potential therapeutic strategy for PARPi-resistant ovarian cancer.
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