ArticleCancer discovery2013
Metabolic and functional genomic studies identify deoxythymidylate kinase as a target in LKB1-mutant lung cancer.
Article in Cancer discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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102 citing papers in PubMed, 151 citations in OpenAlex.
- Molecular insights and therapeutic implications for the tumor suppressor role of LKB1 in non-small cell lung cancer.Cancer letters · 2026Review
- PARP1 Suppression Drives ROS Resistance in Aneuploid Cancer Cells.bioRxiv : the preprint server for biology · 2026Article
- Construction of a novel G2/M checkpoint-related gene signature for prognosis in hepatocellular carcinoma based on machine learning.Discover oncology · 2025Article
- Causality Between Immune Cells, Metabolites and Breast Cancer: Mendelian Randomization and Mediation Analysis.Biochemical genetics · 2025Article
- Transcriptional repression by HDAC3 mediates T cell exclusion fromProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Genome-wide CRISPR screens in spheroid culture reveal that the tumor suppressor LKB1 inhibits growth via the PIKFYVE lipid kinase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Metformin promotes anti-tumor immunity inOncology research · 2024Article
- The role of STK11/LKB1 in cancer biology: implications for ovarian tumorigenesis and progression.Frontiers in cell and developmental biology · 2024Review
- Bi-steric mTORC1 inhibitors induce apoptotic cell death in tumor models with hyperactivated mTORC1.The Journal of clinical investigation · 2023Article
- Article
- STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway.Molecular cancer · 2023Article
- MCT4-dependent lactate secretion suppresses antitumor immunity in LKB1-deficient lung adenocarcinoma.Cancer cell · 2023Article
- Histone Deacetylase 6 Inhibition Exploits Selective Metabolic Vulnerabilities in LKB1 Mutant, KRAS Driven NSCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023Article
- The evolving landscape of involvement of DTYMK enzymes in cancer.Medical oncology (Northwood, London, England) · 2023Review
- LKB1 controls inflammatory potential through CRTC2-dependent histone acetylation.Molecular cell · 2023Article
- LKB1-Dependent Regulation of TPI1 Creates a Divergent Metabolic Liability between Human and Mouse Lung Adenocarcinoma.Cancer discovery · 2023Article
- Specific gut microbiome signature predicts hepatitis B virus-related hepatocellular carcinoma patients with microvascular invasion.Annals of medicine · 2023Article
- Identification of a Molecularly-Defined Subset of Breast and Ovarian Cancer Models that Respond to WEE1 or ATR Inhibition, Overcoming PARP Inhibitor Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Causal effects of genetically determined metabolites on cancers included lung, breast, ovarian cancer, and glioma: a Mendelian randomization study.Translational lung cancer research · 2022Article
42 more citing papers are in PubMed but not listed here.
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40 authors at 6 institutions in 1 country.
Funding
Abstract
The LKB1/STK11 tumor suppressor encodes a serine/threonine kinase, which coordinates cell growth, polarity, motility, and metabolism. In non-small cell lung carcinoma, LKB1 is somatically inactivated in 25% to 30% of cases, often concurrently with activating KRAS mutations. Here, we used an integrative approach to define novel therapeutic targets in KRAS-driven LKB1-mutant lung cancers. High-throughput RNA interference screens in lung cancer cell lines from genetically engineered mouse models driven by activated KRAS with or without coincident Lkb1 deletion led to the identification of Dtymk, encoding deoxythymidylate kinase (DTYMK), which catalyzes dTTP biosynthesis, as synthetically lethal with Lkb1 deficiency in mouse and human lung cancer lines. Global metabolite profiling showed that Lkb1-null cells had a striking decrease in multiple nucleotide metabolites as compared with the Lkb1-wild-type cells. Thus, LKB1-mutant lung cancers have deficits in nucleotide metabolism that confer hypersensitivity to DTYMK inhibition, suggesting that DTYMK is a potential therapeutic target in this aggressive subset of tumors.
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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.