ArticleOncotarget2015
Combined inhibition of Chk1 and Wee1 as a new therapeutic strategy for mantle 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 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
- Synthetic Lethal Combinations of DNA Repair Inhibitors and Genotoxic Agents to Target High-Risk Diffuse Large B Cell Lymphoma.Hematological oncology · 2025Article
- Targeting the DNA damage response through TBL1X in mantle cell lymphoma.Blood advances · 2025Article
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Article
- DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities.International journal of molecular sciences · 2022Review
- Targeting cell cycle regulation via the G2-M checkpoint for synthetic lethality in melanoma.Cell cycle (Georgetown, Tex.) · 2021Review
- Article
- A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target.Journal of hematology & oncology · 2020Review
- Role of ETS1 in the Transcriptional Network of Diffuse Large B Cell Lymphoma of the Activated B Cell-Like Type.Cancers · 2020Article
- The therapeutic effectiveness ofLeukemia · 2020Article
- Article
- Coordinately Targeting Cell-Cycle Checkpoint Functions in Integrated Models of Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- An essential role for dNTP homeostasis following CDK-induced replication stress.Journal of cell science · 2019Article
- Kinase inhibitor library screening identifies synergistic drug combinations effective in sensitive and resistant melanoma cells.Journal of experimental & clinical cancer research : CR · 2019Article
- Bromodomain and extra-terminal domain inhibition modulates the expression of pathologically relevant microRNAs in diffuse large B-cell lymphoma.Haematologica · 2018Article
- Combining Ibrutinib with Chk1 Inhibitors Synergistically Targets Mantle Cell Lymphoma Cell Lines.Targeted oncology · 2018Article
- ATR/CHK1 inhibitors and cancer therapy.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2018Review
- Article
- Article
- Directing the use of DDR kinase inhibitors in cancer treatment.Expert opinion on investigational drugs · 2017Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mantle cell lymphoma (MCL) is an aggressive, incurable disease, characterized by a deregulated cell cycle. Chk1 and Wee1 are main regulators of cell cycle progression and recent data on solid tumors suggest that simultaneous inhibition of these proteins has a strong synergistic cytotoxic effect. The effects of a Chk1 inhibitor (PF-00477736) and a Wee1 inhibitor (MK-1775) have been herein investigated in a large panel of mature B-cell lymphoma cell lines. We found that MCL cells were the most sensitive to the Chk1 inhibitor PF-00477736 and Wee1 inhibitor MK-1775 as single agents. Possible involvement of the translocation t(11;14) in Chk1 inhibitor sensitivity was hypothesized. The combined inhibition of Chk1 and Wee1 was strongly synergistic in MCL cells, leading to deregulation of the cell cycle, with increased activity of CDK2 and CDK1, and activation of apoptosis. In vivo treatment with the drug combination of mice bearing JeKo-1 xenografts (MCL) had a marked antitumor effect with tumor regressions observed at non-toxic doses (best T/C%=0.54%). Gene expression profiling suggested effect on genes involved in apoptosis. The strong synergism observed by combining Chk1 and Wee1 inhibitors in preclinical models of MCL provides the rationale for testing this combination in the clinical setting.
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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 OpenQuestion graph.