ArticleOncotarget2015
Wee1 is required to sustain ATR/Chk1 signaling upon replicative stress.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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.
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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
33 citing papers in PubMed, 40 citations in OpenAlex.
- Review
- Unsupervised Deep Representation Learning and Probabilistic Clustering for the Systems-Level Discovery of Germline Mutation Signatures in Pediatric Cancers.Biomedicines · 2026Article
- Therapy as a State-Generator: Dynamic Phenotypic Landscapes and Adaptive Stress Circuits in Chemotherapy Resistance of Breast Cancer.Antioxidants (Basel, Switzerland) · 2026Review
- Overcoming acquired doxorubicin resistance of ovarian carcinoma cells by verapamil‑mediated promotion of DNA damage‑driven cytotoxicity.International journal of oncology · 2026Article
- Targeting ATR-CHK1 and ATM-CHK2 Axes in Pancreatic Cancer-A Comprehensive Review of Literature.International journal of molecular sciences · 2026Review
- High-throughput drug screening identifies EGFR/MAPK pathway targeting sensitivities in organoid models of ovarian carcinosarcoma.Journal of experimental & clinical cancer research : CR · 2026Article
- WEE1 kinase in cancer: Molecular mechanisms and inhibitor insights.EXCLI journal · 2026Review
- Coupling of stemness maintenance with cell cycle control in stem cells.Frontiers in cell and developmental biology · 2025Review
- Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer.Frontiers in oncology · 2024Review
- Therapeutic inhibition of Bmi-1 ablates chemoresistant cancer stem cells in adenoid cystic carcinoma.Oral oncology · 2023Article
- The Landscape and Therapeutic Targeting ofCurrent issues in molecular biology · 2023Review
- Pharmacologic Induction of BRCAness inCancers · 2022Review
- Cell cycle checkpoints and beyond: Exploiting the ATR/CHK1/WEE1 pathway for the treatment of PARP inhibitor-resistant cancer.Pharmacological research · 2022Review
- Effects of Wee1 inhibitor adavosertib on patient-derived high-grade serous ovarian cancer cells are multiple and independent of homologous recombination status.Frontiers in oncology · 2022Article
- Therapeutic resistance in pancreatic ductal adenocarcinoma: Current challenges and future opportunities.World journal of gastroenterology · 2021Review
- Review
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- The translational repressor 4E-BP1 regulates RRM2 levels and functions as a tumor suppressor in Ewing sarcoma tumors.Oncogene · 2021Article
- Review
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Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The therapeutic efficacy of nucleoside analogues, e.g. gemcitabine, against cancer cells can be augmented by inhibitors of checkpoint kinases, including Wee1, ATR, and Chk1. We have compared the chemosensitizing effect of these inhibitors in cells derived from pancreatic cancer, a tumor entity where gemcitabine is part of the first-line therapeutic regimens, and in osteosarcoma-derived cells. As expected, all three inhibitors rendered cancer cells more sensitive to gemcitabine, but Wee1 inhibition proved to be particularly efficient in this context. Investigating the reasons for this potent sensitizing effect, we found that Wee1 inhibition or knockdown not only blocked Wee1 activity, but also reduced the activation of ATR/Chk1 in gemcitabine-treated cells. Combination of several inhibitors revealed that Wee1 inhibition requires Cyclin-dependent kinases 1 and 2 (Cdk1/2) and Polo-like kinase 1 (Plk1) to reduce ATR/Chk1 activity. Through activation of Cdks and Plk1, Wee1 inhibition reduces Claspin and CtIP levels, explaining the impairment in ATR/Chk1 activity. Taken together, these results confer a consistent signaling pathway reaching from Wee1 inhibition to impaired Chk1 activity, mechanistically dissecting how Wee1 inhibitors not only dysregulate cell cycle progression, but also enhance replicative stress and chemosensitivity towards nucleoside analogues.
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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.