ArticleOncogene2024
Synthetic lethal combination of CHK1 and WEE1 inhibition for treatment of castration-resistant prostate cancer.
Article in Oncogene, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 13 citations in OpenAlex.
- Rethinking the role of synergy calculations in the next century of drug combination discovery.Med (New York, N.Y.) · 2026Review
- CHK1 and CHK2 as Context-Dependent Rheostats of Genotoxic Stress: Implications for Cell Fate and Tumor Immunity.International journal of biological sciences · 2026Review
- Research progress of DNA damage repair (DDR) and DDR inhibitors in tumor immunotherapy.World journal of surgical oncology · 2025Review
- Lysine demethylase 5D promotes CHEK1 inhibitor sensitivity through p38-mediated cyclooxygenase-2 expression in castration-resistant prostate cancer cells.The Journal of pharmacology and experimental therapeutics · 2025Article
- Combined CHK1 and PD-L1 blockade as a novel therapeutic strategy against stemness and immunosuppression in ovarian cancer.Cancer immunology, immunotherapy : CII · 2025Article
- Myc family proteins: Molecular drivers of tumorigenesis and resistance in neuroendocrine tumors.Biochimica et biophysica acta. Reviews on cancer · 2025Review
- Article
- Cancer Vulnerabilities Through Targeting the ATR/Chk1 and ATM/Chk2 Axes in the Context of DNA Damage.Cells · 2025Review
- Perspectives on cancer therapy-synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challenges.Cell death discovery · 2025Review
- Effect of PRKD3 on cell cycle in gastric cancer progression and downstream regulatory networks.Medical oncology (Northwood, London, England) · 2025Article
- SORBS1 Knockdown Resists S/G2 Arrest and Apoptosis Caused by Polyphyllin H-Induced DNA Damage in Pancreatic Cancer.Oncology research · 2025Article
- CHK1 inhibition overcomes gemcitabine resistance in non-small cell lung cancer cell A549.Molecular & cellular oncology · 2025Article
- GSFM: A genome-scale functional module transformation to represent drug efficacy forActa pharmaceutica Sinica. B · 2025Article
- The Pivotal Role of Preclinical Animal Models in Anti-Cancer Drug Discovery and Personalized Cancer Therapy Strategies.Pharmaceuticals (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
WEE1 and CHEK1 (CHK1) kinases are critical regulators of the G2/M cell cycle checkpoint and DNA damage response pathways. The WEE1 inhibitor AZD1775 and the CHK1 inhibitor SRA737 are in clinical trials for various cancers, but have not been thoroughly examined in prostate cancer, particularly castration-resistant (CRPC) and neuroendocrine prostate cancers (NEPC). Our data demonstrated elevated WEE1 and CHK1 expressions in CRPC and NEPC cell lines and patient samples. AZD1775 resulted in rapid and potent cell killing with comparable IC50s across different prostate cancer cell lines, while SRA737 displayed time-dependent progressive cell killing with 10- to 20-fold differences in IC50s. Notably, their combination synergistically reduced the viability of all CRPC cell lines and tumor spheroids in a concentration- and time-dependent manner. Importantly, in a transgenic mouse model of NEPC, both agents alone or in combination suppressed tumor growth, improved overall survival, and reduced the incidence of distant metastases, with SRA737 exhibiting remarkable single agent anticancer activity. Mechanistically, SRA737 synergized with AZD1775 by blocking AZD1775-induced feedback activation of CHK1 in prostate cancer cells, resulting in increased mitotic entry and accumulation of DNA damage. In summary, this preclinical study shows that CHK1 inhibitor SRA737 alone and its combination with AZD1775 offer potential effective treatments for CRPC and NEPC.
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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.