ArticleJournal of hematology & oncology2018
Targeting WEE1 to enhance conventional therapies for acute lymphoblastic leukemia.
Article in Journal of hematology & oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 56 citations in OpenAlex.
- An update of predictive biomarkers related to WEE1 inhibition in cancer therapy.Journal of cancer research and clinical oncology · 2024Pooled it
- A Systematic Review of Candidate miRNAs, Its Targeted Genes and Pathways in Chronic Myeloid Leukemia-An Integrated Bioinformatical Analysis.Frontiers in oncology · 2022Pooled it
- Discovery of molecularly-informed therapeutic strategies for mature T-cell leukemias and lymphomas.Blood advances · 2025Article
- Therapeutic potential of targeting the FLNA-regulated Wee1 kinase in adrenocortical carcinomas.International journal of cancer · 2025Article
- WEE Family Kinase Inhibitors Combined with Sorafenib Can Selectively Inhibit HCC Cell Proliferation.Current cancer drug targets · 2025Article
- Applications of Modified Mesenchymal Stem Cells as Targeted Systems against Tumor Cells.International journal of molecular sciences · 2024Review
- Sequential drug treatment targeting cell cycle and cell fate regulatory programs blocks non-genetic cancer evolution in acute lymphoblastic leukemia.Genome biology · 2024Article
- Targeting RNA N6-methyladenosine modification-- a novel therapeutic target for HER2- positive gastric cancer.Frontiers in oncology · 2024Article
- Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer.Frontiers in oncology · 2024Review
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Synergistic interactions of cytarabine-adavosertib in leukemic cell lines proliferation and metabolomic endpoints.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Bortezomib Is Effective in the Treatment of T Lymphoblastic Leukaemia by Inducing DNA Damage, WEE1 Downregulation, and Mitotic Catastrophe.International journal of molecular sciences · 2023Article
- Exploring the ATR-CHK1 pathway in the response of doxorubicin-induced DNA damages in acute lymphoblastic leukemia cells.Cell biology and toxicology · 2023Article
- The Implication of Topoisomerase II Inhibitors in Synthetic Lethality for Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Article
- CRLF2 overexpression results in reduced B-cell differentiation and upregulated E2F signaling in the Dp16 mouse model of Down syndrome.Experimental hematology · 2022Article
- Polo-like kinase-1, Aurora kinase A and WEE1 kinase are promising druggable targets in CML cells displaying BCR::ABL1-independent resistance to tyrosine kinase inhibitors.Frontiers in oncology · 2022Article
- The DNA damage repair-related geneTranslational lung cancer research · 2021Article
- WEE1 inhibition induces glutamine addiction in T-cell acute lymphoblastic leukemia.Haematologica · 2021Article
- Sensitizing multidrug-resistant leukemia cells to common cytostatics by an aluminium-salen complex that has high-apoptotic effects in leukemia, lymphoma and mamma carcinoma cells.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundDespite the recent progress that has been made in the understanding and treatment of acute lymphoblastic leukemia (ALL), the outcome is still dismal in adult ALL cases. Several studies in solid tumors identified high expression of WEE1 kinase as a poor prognostic factor and reported its role as a cancer-conserving oncogene that protects cancer cells from DNA damage. Therefore, the targeted inhibition of WEE1 kinase has emerged as a rational strategy to sensitize cancer cells to antineoplastic compounds, which we evaluate in this study.
methodsThe effectiveness of the selective WEE1 inhibitor AZD-1775 as a single agent and in combination with different antineoplastic agents in B and T cell precursor ALL (B/T-ALL) was evaluated in vitro and ex vivo studies. The efficacy of the compound in terms of cytotoxicity, induction of apoptosis, and changes in gene and protein expression was assessed using different B/T-ALL cell lines and confirmed in primary ALL blasts.
resultsWe showed that WEE1 was highly expressed in adult primary ALL bone marrow and peripheral blood blasts (n = 58) compared to normal mononuclear cells isolated from the peripheral blood of healthy donors (p = 0.004). Thus, we hypothesized that WEE1 could be a rational target in ALL, and its inhibition could enhance the cytotoxicity of conventional therapies used for ALL. We evaluated the efficacy of AZD-1775 as a single agent and in combination with several antineoplastic agents, and we elucidated its mechanisms of action. AZD-1775 reduced cell viability in B/T-ALL cell lines by disrupting the G2/M checkpoint and inducing apoptosis. These findings were confirmed in human primary ALL bone marrow and peripheral blood blasts (n = 15). In both cell lines and primary leukemic cells, AZD-1775 significantly enhanced the efficacy of several tyrosine kinase inhibitors (TKIs) such as bosutinib, imatinib, and ponatinib, and of chemotherapeutic agents (clofarabine and doxorubicin) in terms of the reduction of cell viability, apoptosis induction, and inhibition of proliferation.
conclusionsOur data suggest that WEE1 plays a role in ALL blast's survival and is a bona fide target for therapeutic intervention. These data support the evaluation of the therapeutic potential of AZD-1775 as chemo-sensitizer agent for the treatment of B/T-ALL.
Indexed as
Identifiers
What OpenQuestion holds
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.