ArticleCancer science2021
WEE1 inhibitor and ataxia telangiectasia and RAD3-related inhibitor trigger stimulator of interferon gene-dependent immune response and enhance tumor treatment efficacy through programmed death-ligand 1 blockade.
Article in Cancer science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Selective Macrocyclic WEE1 Kinase Inhibitors with Strong Efficacy against Patient-Derived Colorectal Cancer Organoids.Journal of medicinal chemistry · 2026Article
- ATR kinase inhibitors induce mitochondrial fission in CD8bioRxiv : the preprint server for biology · 2026Article
- Next Generation DNA Damage Response Inhibitors: Harnessing Nanocarriers and Tumor Microenvironment for Precision Cancer Therapy.Oncology research · 2026Review
- Targeting synthetic lethality in colorectal cancer.Chinese medical journal · 2025Article
- Synthetic lethality in cancer: a protocol for scoping review of gene interactions from synthetic lethal screens and functional studies.Systematic reviews · 2025Article
- cGAS/STING signaling pathway in gynecological malignancies: From molecular mechanisms to therapeutic values.Frontiers in immunology · 2025Review
- DNA repair-dependent immunogenic liabilities in colorectal cancer: opportunities from errors.British journal of cancer · 2024Review
- Targeting ATR in patients with cancer.Nature reviews. Clinical oncology · 2024Review
- Targeting WEE1 Kinase in Gynecological Malignancies.Drug design, development and therapy · 2024Review
- Treatment for ovarian clear cell carcinoma with combined inhibition of WEE1 and ATR.Journal of ovarian research · 2023Article
- Could Inhibiting the DNA Damage Repair Checkpoint Rescue Immune-Checkpoint-Inhibitor-Resistant Endometrial Cancer?Journal of clinical medicine · 2023Review
- The schedule of ATR inhibitor AZD6738 can potentiate or abolish antitumor immune responses to radiotherapy.JCI insight · 2023Article
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- Correlation between IL3 signaling pathway-related genes and immune checkpoint inhibitor efficacy in patients with renal cell carcinoma.Cancer biomarkers : section A of Disease markers · 2023Article
- ATR Inhibitors in Platinum-Resistant Ovarian Cancer.Cancers · 2022Review
- WEE1 inhibition enhances the antitumor immune response to PD-L1 blockade by the concomitant activation of STING and STAT1 pathways in SCLC.Cell reports · 2022Article
- Recent Advances in Synergistic Antitumor Effects Exploited from the Inhibition of Ataxia Telangiectasia and RAD3-Related Protein Kinase (ATR).Molecules (Basel, Switzerland) · 2022Review
- Enhancing anti-tumour innate immunity by targeting the DNA damage response and pattern recognition receptors in combination with radiotherapy.Frontiers in oncology · 2022Review
- Ferroptosis synergistically sensitizes wee1 inhibitors: a bibliometric study.American journal of translational research · 2022Article
- Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
WEE1 plays an important role in the regulation of cell cycle G2/M checkpoints and DNA damage response (DDR). Inhibition of WEE1 can increase the instability of the genome and have anti-tumor effects in some solid tumors. However, it has certain limitations for multiple cancer cells from different lineages. Therefore, we consider the use of synthetic lethal interactions to enhance the therapeutic effect. Our experiments proved that WEE1 inhibitor (WEE1i) can activate the ataxia telangiectasia and RAD3-related (ATR) pathway and that blockage of ATR dramatically sensitized the WEE1i-induced cell death. The tumor-selective synthetic lethality between bioavailable WEE1 and ATR inhibitors led to tumor remission in vivo. Mechanistically, the combination promoted the accumulation of cytosolic double-strand DNA, which subsequently activated the stimulator of the interferon gene (STING) pathway and induced the production of type I interferon and CD8+ T cells, thereby inducing anti-tumor immunity. Furthermore, our study found that immune checkpoint programmed death-ligand 1 is upregulated by the combination therapy, and blocking PD-L1 further enhances the effect of the combination therapy. In summary, as an immunomodulator, the combination of WEE1i with ATR inhibitor (ATRi) and immune checkpoint blockers provides a potential new approach for cancer treatment.
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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.