ArticleOncotarget2015
Constitutive activation of the DNA damage response pathway as a novel therapeutic target in diffuse large B-cell lymphoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 58 citations in OpenAlex.
- Dual targeting of the DNA damage response pathway and BCL-2 in diffuse large B-cell lymphoma.Leukemia · 2022Trial
- Targeting DNA interstrand crosslinks repair with synthetic lethality in High-Grade B-Cell Lymphoma.Leukemia · 2026Article
- CHK1 and CHK2 as Context-Dependent Rheostats of Genotoxic Stress: Implications for Cell Fate and Tumor Immunity.International journal of biological sciences · 2026Review
- BANF1 at the crossroads of genome stability and innate immunity: emerging implications for hematologic malignancies.Frontiers in immunology · 2026Review
- Multi-omics and experimental validation reveal mechanism of compound mylabris capsules in treating diffuse large B-cell lymphoma.Scientific reports · 2025Article
- The art of war: using genetic insights to understand and harness radiation sensitivity in hematologic malignancies.Frontiers in oncology · 2024Review
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Potential Pathogenic Impact of Cow's Milk Consumption and Bovine Milk-Derived Exosomal MicroRNAs in Diffuse Large B-Cell Lymphoma.International journal of molecular sciences · 2023Review
- Nuclear pCHK1 as a potential biomarker of increased sensitivity to ATR inhibition.The Journal of pathology · 2023Article
- Studying the DNA damage response pathway in hematopoietic canine cancer cell lines, a necessary step for finding targets to generate new therapies to treat cancer in dogs.Frontiers in veterinary science · 2023Article
- ATR-mediated DNA damage responses underlie aberrant B cell activity in systemic lupus erythematosus.Science advances · 2022Article
- The SKP2-p27 axis defines susceptibility to cell death upon CHK1 inhibition.Molecular oncology · 2022Article
- Hsp90 inhibition sensitizes DLBCL cells to cisplatin.Cancer chemotherapy and pharmacology · 2022Article
- Targeting the DNA Damage Response to Increase Anthracycline-Based Chemotherapy Cytotoxicity in T-Cell Lymphoma.International journal of molecular sciences · 2022Article
- Identification and Validation of a DNA Damage Repair-Related Signature for Diffuse Large B-Cell Lymphoma.BioMed research international · 2022Article
- Article
- Beclin1‑armed oncolytic Vaccinia virus enhances the therapeutic efficacy of R‑CHOP against lymphoma in vitro and in vivo.Oncology reports · 2021Observational
- Characterization of G-quadruplex antibody reveals differential specificity for G4 DNA forms.DNA research : an international journal for rapid publication of reports on genes and genomes · 2020Article
- WEE1 inhibition synergizes with CHOP chemotherapy and radiation therapy through induction of premature mitotic entry and DNA damage in diffuse large B-cell lymphoma.Therapeutic advances in hematology · 2020Article
- CRISPR/Cas9-Mediated Foxp1 Silencing Restores Immune Surveillance in an Immunocompetent A20 Lymphoma Model.Frontiers in oncology · 2020Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The recent finding that MYC-driven cancers are sensitive to inhibition of the DNA damage response (DDR) pathway, prompted us to investigate the role of DDR pathway as therapeutic target in diffuse large B-cell lymphoma (DLBCL), which frequently overexpresses the MYC oncogene. In a preliminary immunohistochemical study conducted on 99 consecutive DLBCL patients, we found that about half of DLBCLs showed constitutive expression of the phosphorylated forms of checkpoint kinases (CHK) and CDC25c, markers of DDR activation, and of phosphorylated histone H2AX (γH2AX), marker of DNA damage and genomic instability. Constitutive γH2AX expression correlated with c-MYC levels and DDR activation, and defined a subset of tumors characterised by poor outcome. Next, we used the CHK inhibitor PF-0477736 as a tool to investigate whether the inhibition of the DDR pathway might represent a novel therapeutic approach in DLBCL. Submicromolar concentrations of PF-0477736 hindered proliferation in DLBCL cell lines with activated DDR pathway. These results were fully recapitulated with a different CHK inhibitor (AZD-7762). Inhibition of checkpoint kinases induced rapid DNA damage accumulation and apoptosis in DLBCL cell lines and primary cells. These data suggest that pharmacologic inhibition of DDR through targeting of CHK kinases may represent a novel therapeutic strategy in DLBCL.
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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.