ArticleDrug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy2024
Syk-dependent homologous recombination activation promotes cancer resistance to DNA targeted therapy.
Article in Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 15 citations in OpenAlex.
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Troxerutin suppresses the stemness of hepatocellular carcinoma via the Syk/FOXO3 feedback loop.Cell biology and toxicology · 2026Article
- PARP inhibitors in the treatment of ovarian cancer: a narrative review.Translational cancer research · 2026Review
- Disrupting USP14-mediated PARP1 dynamics reinstates MIC-A/B-driven antigen-independent CD8Science advances · 2026Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- The potential role of lily polysaccharide in mitigating radiation-induced pneumonitis via the gut-lung axis: a comprehensive review.Frontiers in pharmacology · 2026Review
- Targeting SYK enhances responses to radiotherapy and PD-1 blockade with myeloid immune remodeling in breast cancer.Frontiers in immunology · 2026Article
- Targeting fatty acid synthase to overcome PARP inhibitor resistance and to create an artificial synthetic lethality for triple-negative breast cancer.Genes & diseases · 2026Article
- Chimeric RNAs as Novel Neoantigens for Extracellular Vesicles-Based Vaccines Against Cancer.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Phosphorylation of RNF213 by ATM-mediated ubiquitination of RPA1 regulates homologous recombination repair and chemosensitivity.Cell death & disease · 2025Article
- AZD5153 enhances the chemo-sensitivity of gemcitabine on pancreatic cancer cells in vitro and in vivo.Cancer cell international · 2025Article
- Neutrophil diversity and function in health and disease.Signal transduction and targeted therapy · 2024Review
- New insights into SYK targeting in solid tumors.Trends in pharmacological sciences · 2024Review
- Identification of circadian clock-related immunological prognostic index and molecular subtypes in prostate cancer.Discover oncology · 2024Article
- Molecular mechanism of PARP inhibitor resistance.Oncoscience · 2024Review
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
Enhanced DNA repair is an important mechanism of inherent and acquired resistance to DNA targeted therapies, including poly ADP ribose polymerase (PARP) inhibition. Spleen associated tyrosine kinase (Syk) is a non-receptor tyrosine kinase acknowledged for its regulatory roles in immune cell function, cell adhesion, and vascular development. This study presents evidence indicating that Syk expression in high-grade serous ovarian cancer and triple-negative breast cancers promotes DNA double-strand break resection, homologous recombination (HR), and subsequent therapeutic resistance. Our investigations reveal that Syk is activated by ATM following DNA damage and is recruited to DNA double-strand breaks by NBS1. Once localized to the break site, Syk phosphorylates CtIP, a pivotal mediator of resection and HR, at Thr-847 to promote repair activity, particularly in Syk-expressing cancer cells. Inhibition of Syk or its genetic deletion impedes CtIP Thr-847 phosphorylation and overcomes the resistant phenotype. Collectively, our findings suggest a model wherein Syk fosters therapeutic resistance by promoting DNA resection and HR through a hitherto uncharacterized ATM-Syk-CtIP pathway. Moreover, Syk emerges as a promising tumor-specific target to sensitize Syk-expressing tumors to PARP inhibitors, radiation and other DNA-targeted therapies.
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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 Socratic graph.