ArticleScientific reports2017
Modification of tumour cell metabolism modulates sensitivity to Chk1 inhibitor-induced DNA damage.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Chloroquine Potentiates the Chemotherapeutic Effect of Carboplatin and ATR/Chk1 Inhibitors by Increasing the Replication Stress.International journal of molecular sciences · 2026Article
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche.Frontiers in oncology · 2022Review
- Triple Isozyme Lactic Acid Dehydrogenase Inhibition in Fully Viable MDA-MB-231 Cells Induces Cytostatic Effects That Are Not Reversed by Exogenous Lactic Acid.Biomolecules · 2021Article
- LDHA is enriched in human islet alpha cells and upregulated in type 2 diabetes.Biochemical and biophysical research communications · 2021Article
- Dissecting the early steps of MLL induced leukaemogenic transformation using a mouse model of AML.Nature communications · 2020Article
- Metabolic plasticity imparts erlotinib-resistance in pancreatic cancer by upregulating glucose-6-phosphate dehydrogenase.Cancer & metabolism · 2020Article
- The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage.Aging · 2019Article
- Chk1 loss creates replication barriers that compromise cell survival independently of excess origin firing.The EMBO journal · 2019Article
- Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- A high content, high throughput cellular thermal stability assay for measuring drug-target engagement in living cells.PloS one · 2018Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chk1 kinase inhibitors are currently under clinical investigation as potentiators of cytotoxic chemotherapy and demonstrate potent activity in combination with anti-metabolite drugs that increase replication stress through the inhibition of nucleotide or deoxyribonucleotide biosynthesis. Inhibiting other metabolic pathways critical for the supply of building blocks necessary to support DNA replication may lead to increased DNA damage and synergy with an inhibitor of Chk1. A screen of small molecule metabolism modulators identified combinatorial activity between a Chk1 inhibitor and chloroquine or the LDHA/LDHB inhibitor GSK 2837808A. Compounds, such as 2-deoxyglucose or 6-aminonicotinamide, that reduced the fraction of cells undergoing active replication rendered tumour cells more resistant to Chk1 inhibitor-induced DNA damage. Withdrawal of glucose or glutamine induced G1 and G2/M arrest without increasing DNA damage and reduced Chk1 expression and activation through autophosphorylation. This suggests the expression and activation of Chk1 kinase is associated with cells undergoing active DNA replication. Glutamine starvation rendered tumour cells more resistant to Chk1 inhibitor-induced DNA damage and reversal of the glutamine starvation restored the sensitivity of tumour cells to Chk1 inhibitor-induced DNA damage. Chk1 inhibitors may be a potentially useful therapeutic treatment for patients whose tumours contain a high fraction of replicating cells.
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Registered trials
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