ArticleJournal of experimental & clinical cancer research : CR2023
Dual inhibition of CDK12 and CDK13 uncovers actionable vulnerabilities in patient-derived ovarian cancer organoids.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Expanding Synthetic Lethality in DNA Damage Response-Defective Cancers Through Stress Phenotype-Guided Kinase Targeting.International journal of molecular sciences · 2026Review
- CDK12/13 inhibition overcomes platinum resistance by impairing RNA metabolism.Signal transduction and targeted therapy · 2026Article
- U2 snRNP inhibition hampers pancreatic cancer cell viability by disrupting DNA repair proficiency and mitotic checkpoint integrity.Journal of experimental & clinical cancer research : CR · 2026Article
- Inhibition of cyclin-dependent kinases 12/13 using CT7439 as a treatment for colorectal cancer with CDK12 upregulation.Molecular oncology · 2026Article
- Rethinking ovarian cancer III: the past decade and future directions.Nature reviews. Cancer · 2026Review
- HnRNP C binding to invertedScience advances · 2026Article
- Absence of synergistic effects by CDK12/13 inhibition in combination with cisplatin or olaparib in ovarian cancer cells.Scientific reports · 2026Article
- Targeting CDK12/13 Drives Mitotic Arrest to Overcome Resistance to KRASG12C Inhibitors.Cancer research · 2026Article
- CDK12 and CDK13 in oncology: from RNA regulation to therapeutic targeting.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- New insights into the dule roles CDK12 in human cancers: Mechanisms and interventions for cancer therapy.Journal of pharmaceutical analysis · 2025Review
- Defining CDK12 as a tumor suppressor and therapeutic target in mouse models of tubo-ovarian high-grade serous carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mechanistic Roles of Transcriptional Cyclin-Dependent Kinases in Oncogenesis: Implications for Cancer Therapy.Cancers · 2025Review
- Physiological and pathological roles of the transcriptional kinases CDK12 and CDK13 in the central nervous system.Cell death and differentiation · 2025Review
- Organoid development and applications in gynecological cancers: the new stage of tumor treatment.Journal of nanobiotechnology · 2025Review
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Exploration of organoids in ovarian cancer: From basic research to clinical translation.Translational oncology · 2024Review
- CDK12 loss drives prostate cancer progression, transcription-replication conflicts, and synthetic lethality with paralog CDK13.Cell reports. Medicine · 2024Article
- Organoid modeling meets cancers of female reproductive tract.Cell death discovery · 2024Review
- The use of organoids in creating immune microenvironments and treating gynecological tumors.Journal of translational medicine · 2024Review
- Phenotyping Tumor Heterogeneity through Proteogenomics: Study Models and Challenges.International journal of molecular sciences · 2024Review
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundHigh grade serous ovarian cancer (HGSOC) is highly lethal, partly due to chemotherapy resistance and limited availability of targeted approaches. Cyclin dependent kinases 12 and 13 (CDK12/13) are promising therapeutic targets in human cancers, including HGSOC. Nevertheless, the effects of their inhibition in HGSOC and the potential synergy with other drugs are poorly known.
methodsWe analyzed the effects of the CDK12/13 inhibitor THZ531 in HGSOC cells and patient-derived organoids (PDOs). RNA sequencing and quantitative PCR analyses were performed to identify the genome-wide effects of short-term CDK12/13 inhibition on the transcriptome of HGSOC cells. Viability assays with HGSOC cells and PDOs were performed to assess the efficacy of THZ531 as single agent or in combination with clinically relevant drugs.
resultsThe CDK12 and CDK13 genes are deregulated in HGSOC and their concomitant up-regulation with the oncogene MYC predicts poor prognosis. HGSOC cells and PDOs display high sensitivity to CDK12/13 inhibition, which synergizes with drugs in clinical use for HGSOC. Transcriptome analyses revealed cancer-relevant genes whose expression is repressed by dual CDK12/13 inhibition through impaired splicing. Combined treatment with THZ531 and inhibitors of pathways regulated by these cancer relevant genes (EGFR, RPTOR, ATRIP) exerted synergic effects on HGSOC PDO viability.
conclusionsCDK12 and CDK13 represent valuable therapeutic targets for HGSOC. We uncovered a wide spectrum of CDK12/13 targets as potential therapeutic vulnerabilities for HGSOC. Moreover, our study indicates that CDK12/13 inhibition enhances the efficacy of approved drugs that are already in use for HGSOC or other human 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.