Trial reportNature communications2022
CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer.
Trial report in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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
28 citing papers in PubMed, 43 citations in OpenAlex.
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Targeting CDK12 disrupts estrogen-receptor chromatin recruitment and ER-MED1 transcription in advanced ER+ breast cancer.Journal of the National Cancer Institute · 2026Article
- Spatial molecular analyses reveal key features associated with response to KN026 in advanced HER2-positive breast cancer.British journal of cancer · 2026Article
- CDK12 regulates cellular metabolism to promote glioblastoma growth.JCI insight · 2025Article
- Targeting Transcriptional Cyclin-Dependent Kinases in Cancer.Molecular cancer therapeutics · 2025Review
- Serine-Driven Metabolic Plasticity Drives Adaptive Resilience in Pancreatic Cancer Cells.Antioxidants (Basel, Switzerland) · 2025Article
- New insights into the dule roles CDK12 in human cancers: Mechanisms and interventions for cancer therapy.Journal of pharmaceutical analysis · 2025Review
- Transcriptional and epigenetic rewiring by the NUP98::KDM5A fusion oncoprotein directly activates CDK12.Nature communications · 2025Article
- Cr3a, a candidate gene conferring fruit cracking resistance, was fine-mapped in an introgression line of Solanum lycopersicum L.The Plant journal : for cell and molecular biology · 2025Article
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Metabolic Reprogramming at the Edge of Redox: Connections Between Metabolic Reprogramming and Cancer Redox State.International journal of molecular sciences · 2025Review
- Development of CDK12 as a Cancer Therapeutic Target and Related Inhibitors.Current cancer drug targets · 2025Review
- Multimodal diagnostic models and subtype analysis for neoadjuvant therapy in breast cancer.Frontiers in immunology · 2025Article
- Screening of a kinase inhibitor library identified novel targetable kinase pathways in triple-negative breast cancer.Anti-cancer drugs · 2025Article
- Loss of NUMB drives aggressive bladder cancer via a RHOA/ROCK/YAP signaling axis.Nature communications · 2024Article
- Cancer cell stiffening via CoQNature communications · 2024Article
- Unveiling the Therapeutic Potential of Folate-Dependent One-Carbon Metabolism in Cancer and Neurodegeneration.International journal of molecular sciences · 2024Review
- CDK12 controls transcription at damaged genes and prevents MYC-induced transcription-replication conflicts.Nature communications · 2024Article
- De Novo Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression.Cancer research communications · 2024Article
- Cyclin-dependent kinase 12 deficiency reprogrammes cellular metabolism to alleviate ferroptosis potential and promote the progression of castration-resistant prostate cancer.Clinical and translational medicine · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclin-dependent kinase 12 (CDK12) overexpression is implicated in breast cancer, but whether it has a primary or only a cooperative tumorigenic role is unclear. Here, we show that transgenic CDK12 overexpression in the mouse mammary gland per se is sufficient to drive the emergence of multiple and multifocal tumors, while, in cooperation with known oncogenes, it promotes earlier tumor onset and metastasis. Integrative transcriptomic, metabolomic and functional data reveal that hyperactivation of the serine-glycine-one-carbon network is a metabolic hallmark inherent to CDK12-induced tumorigenesis. Consistently, in retrospective patient cohort studies and in patient-derived xenografts, CDK12-overexpressing breast tumors show positive response to methotrexate-based chemotherapy targeting CDK12-induced metabolic alterations, while being intrinsically refractory to other types of chemotherapy. In a retrospective analysis of hormone receptor-negative and lymph node-positive breast cancer patients randomized in an adjuvant phase III trial to 1-year low-dose metronomic methotrexate-based chemotherapy or no maintenance chemotherapy, a high CDK12 status predicts a dramatic reduction in distant metastasis rate in the chemotherapy-treated vs. not-treated arm. Thus, by coupling tumor progression with metabolic reprogramming, CDK12 creates an actionable vulnerability for breast cancer therapy and might represent a suitable companion biomarker for targeted antimetabolite therapies in human breast cancers.
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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.