ArticleLeukemia2024
CTPS1 is a novel therapeutic target in multiple myeloma which synergizes with inhibition of CHEK1, ATR or WEE1.
Article in Leukemia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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
19 citing papers in PubMed, 20 citations in OpenAlex.
- Matrine Suppresses Lung Cancer Progression via Dual Inhibition of CHEK1-Mediated DNA Damage Repair and PI3K/AKT Survival Signaling.Thoracic cancer · 2026Article
- CTPS1 promotes lung adenocarcinoma progression as a targetable vulnerability.British journal of cancer · 2026Article
- Metabolic heterogeneity and niche rewiring in bone marrow plasma cells from patients with MGUS, solitary bone plasmacytoma and multiple myeloma.Blood cancer journal · 2026Article
- Spliceosomal component SNRPE drives cell proliferation by regulating CTP synthase 1 mRNA splicing in ovarian cancer.Oncogene · 2026Article
- CTPS1 modulates mitophagy to propel diffuse large B-cell lymphoma via reshaping CEPT1-mediated phospholipid metabolism.Redox biology · 2026Article
- Metabolic Heterogeneity and Niche Rewiring in Plasma Cells are Associated with Progression from MGUS to Multiple Myeloma.Research square · 2026Article
- CTPS1 is an unexplored vulnerability in breast and ovarian cancer.Theranostics · 2026Article
- NEDD4 regulates VEGF signaling and mTOR to promote angiogenesis and the cell cycle in steroid‑induced osteonecrosis of the femoral head.Molecular medicine reports · 2026Article
- CTPS2 regulates CTP synthetase activity by interacting with CTPS1.Life science alliance · 2025Article
- Chromatin relaxation dynamics and histone PTMs in the early DNA damage response.Cancer biology & medicine · 2025Article
- Article
- Effect of PRKD3 on cell cycle in gastric cancer progression and downstream regulatory networks.Medical oncology (Northwood, London, England) · 2025Article
- High WEE1 expression is independently linked to poor survival in multiple myeloma.Blood cancer journal · 2025Article
- Combined inhibition of CTPS1 and ATR is a metabolic vulnerability in p53-deficient myeloma cells.HemaSphere · 2024Article
- High WEE1 expression is independently linked to poor survival in multiple myeloma.bioRxiv : the preprint server for biology · 2024Article
- The Impact of Developmental and Metabolic Cues on Cytoophidium Formation.International journal of molecular sciences · 2024Review
- Article
- Inactivation of cytidine triphosphate synthase 1 prevents fatal auto-immunity in mice.Nature communications · 2024Article
- The emerging roles of glutamine amidotransferases in metabolism and immune defense.Nucleosides, nucleotides & nucleic acids · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeting nucleotide biosynthesis is a proven strategy for the treatment of cancer but is limited by toxicity, reflecting the fundamental nucleotide requirement of dividing cells. The rate limiting step in de novo pyrimidine synthesis is of interest, being catalyzed by two homologous enzymes, CTP synthase 1 (CTPS1) and CTPS2, that could be differentially targeted. Herein, analyses of publicly available datasets identified an essential role for CTPS1 in multiple myeloma (MM), linking high expression of CTPS1 (but not CTPS2) with advanced disease and poor outcomes. In cellular experiments, CTPS1 knockout induced apoptosis of MM cell lines. Exposure of MM cells to STP-B, a novel and highly selective pharmacological inhibitor of CTPS1, inhibited proliferation, induced S phase arrest and led to cell death by apoptosis. Mechanistically, CTPS1 inhibition by STP-B activated DNA damage response (DDR) pathways and induced double-strand DNA breaks which accumulated in early S phase. Combination of STP-B with pharmacological inhibitors of key components of the DDR pathway (ATR, CHEK1 or WEE1) resulted in synergistic growth inhibition and early apoptosis. Taken together, these findings identify CTPS1 as a promising new target in MM, either alone or in combination with DDR pathway inhibition.
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.