ArticleCancer research2022
Combined Inactivation of CTPS1 and ATR Is Synthetically Lethal to MYC-Overexpressing Cancer Cells.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 53 citations in OpenAlex.
- Synthetic lethality targets in pancreatic ductal adenocarcinoma: prevalence and limitations of liquid biopsy detection in a minority-serving cancer center.Future oncology (London, England) · 2026Article
- EphB4 inhibition defines a druggable synthetic-lethal vulnerability in MYC-driven triple-negative breast cancer.Cell death & disease · 2026Article
- CTPS1 modulates mitophagy to propel diffuse large B-cell lymphoma via reshaping CEPT1-mediated phospholipid metabolism.Redox biology · 2026Article
- Hybrid tuned deep learning model for breast cancer diagnosis using genetic data.Scientific reports · 2026Article
- Deciphering the MYCN-driven metabolic microenvironment of neuroblastoma.Trends in molecular medicine · 2026Review
- CTPS1 is an unexplored vulnerability in breast and ovarian cancer.Theranostics · 2026Article
- Pathway for the Development of ATR Inhibitors in Pediatric Malignancies: An ACCELERATE Multistakeholder Analysis.JCO precision oncology · 2026Review
- CTPS2 regulates CTP synthetase activity by interacting with CTPS1.Life science alliance · 2025Article
- Comprehensive investigation of the molecular basis of cancer dependencies suggests therapeutic options for breast cancer.Cancer biology & medicine · 2025Article
- Chromatin relaxation dynamics and histone PTMs in the early DNA damage response.Cancer biology & medicine · 2025Article
- [Circ_0000437 promotes proliferation, invasion, migration and epithelial-mesenchymal transition of breast cancer cells by targeting the let-7b-5p/CTPS1 axis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Filamentation of hCTPS1 with CTP.Cell & bioscience · 2025Article
- Article
- Elucidating the Mechanisms of Acquired Palbociclib Resistance via Comprehensive Metabolomics Profiling.Current issues in molecular biology · 2025Article
- Exploiting replication stress for synthetic lethality in MYC-driven cancers.American journal of cancer research · 2025Review
- Structural Basis of Bifunctional CTP/dCTP Synthase.Journal of molecular biology · 2024Article
- Combined inhibition of CTPS1 and ATR is a metabolic vulnerability in p53-deficient myeloma cells.HemaSphere · 2024Article
- Architecture of CTPS filament networks revealed by cryo-electron tomography.Experimental cell research · 2024Article
- The Impact of Developmental and Metabolic Cues on Cytoophidium Formation.International journal of molecular sciences · 2024Review
- The role of cytidine 5'-triphosphate synthetase 1 in metabolic rewiring during epithelial-to-mesenchymal transition in non-small-cell lung cancer.FEBS open bio · 2024Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
The "undruggable" oncogene MYC supports cancer cell proliferation and survival through parallel induction of multiple anabolic processes. Here we find that inhibiting CTP synthase (CTPS) selectively decreases cell viability and induces DNA replication stress in MYC-overexpressing cells. MYC-driven rRNA synthesis caused the selective DNA replication stress upon CTPS inhibition. Combined inhibition of CTPS and ataxia telangiectasia and Rad3-related protein (ATR) is synthetically lethal in MYC-overexpressing cells, promoting cell death in vitro and decreasing tumor growth in vivo. Unexpectedly, interfering with CTPS1 but not CTPS2 is required to induce replication stress in MYC-deregulated cancer cells and consequent cell death in the presence of an ATR inhibitor. These results highlight a specific and key role of CTPS1 in MYC-driven cancer, suggesting that selectively inhibiting CTPS1 in combination with ATR could be a promising strategy to combat disease progression. SIGNIFICANCE: Inhibition of CTPS in MYC-overexpressing cells blocks pyrimidine synthesis while maintaining ribosome synthesis activity to create an anabolic imbalance that induces replication stress, providing a new approach to selectively target MYC-driven cancer. See related commentary by Chabanon and Postel-Vinay, p. 969.
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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.