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    GENE:

    CDK12 (Cyclin dependent kinase 12)

    i
    Other names: CDK12, Cyclin Dependent Kinase 12, Cdc2-Related Kinase, Arginine/Serine-Rich, Cell Division Cycle 2-Related Protein Kinase 7, Cell Division Protein Kinase 12, CDC2-Related Protein Kinase 7, Cyclin-Dependent Kinase 12, CRKRS, CRK7, CDC2 Related Protein Kinase 7, HCDK12, CrkRS, CRKR
    3d
    Clinically actionable alterations in Indian breast cancer patients derived through whole transcriptome sequencing. (PubMed, Indian J Med Res)
    Fusion transcript analysis identified 91 recurrent fusions, including novel partners with ERBB2, MED1, and CDK12, suggesting the possibility of unique molecular events. Interpretation and conclusions This study demonstrates that Indian breast cancer patients exhibit molecular subtypes and actionable mutations comparable to Caucasian cohorts.
    Review • Journal • BRCA Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CDK12 (Cyclin dependent kinase 12) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase)
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    HER-2 positive • TP53 mutation • BRCA2 mutation • ER positive • BRCA1 mutation • PIK3CA mutation • HER-2 expression • PTEN mutation • FGFR2 mutation • AKT1 mutation
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    Prosigna™ Breast Cancer Prognostic Gene Signature Assay
    6d
    Absence of synergistic effects by CDK12/13 inhibition in combination with cisplatin or olaparib in ovarian cancer cells. (PubMed, Sci Rep)
    However, the combination of SR-4835 with cisplatin or olaparib primarily exhibited an additive, not synergistic, effect. In summary, the present findings indicate that CDK12/13 inhibitor SR-4835 has potent anti-cancer effects accompanied by a BRCAness induction, but fails to achieve synergistic effects with cisplatin or olaparib in OC cells.
    Journal • BRCA Biomarker • PARP Biomarker
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    CDK12 (Cyclin dependent kinase 12)
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    Lynparza (olaparib) • cisplatin
    11d
    Inactivation of CDK12 Enhances Mitochondrial Efficiency to Suppress DNA Damage. (PubMed, J Cell Mol Med)
    Finally, we show that dual inhibition of CDK12/13 results in excessive phosphorylation of the DNA damage H2AX in prostate cancer cells but not in our CDK12/13 inhibitor-resistant model system. In brief, we propose that inactivation of CDK12 rewires cellular energy metabolism to suppress DNA damage.
    Journal
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    CDK12 (Cyclin dependent kinase 12) • CDK13 (Cyclin Dependent Kinase 13)
    13d
    CDK12/CDK13 inhibition disrupts transcriptional elongation and replication fork progression in glioblastoma. (PubMed, EMBO Mol Med)
    CDK12/CDK13 inhibition unexpectedly arrests DNA replication and replication fork progression in a manner distinct from the effect of inhibiting other tCDKs. This dramatic arrest precedes DNA damage response activation and cell cycle arrest, directly linking RNAPII elongation to replication fork dynamics and revealing a previously unrecognized dependence of DNA replication on CDK12/CDK13-RNAPII regulation.
    Journal
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    CDK12 (Cyclin dependent kinase 12) • CDK7 (Cyclin Dependent Kinase 7) • CDK13 (Cyclin Dependent Kinase 13)
    14d
    A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors (clinicaltrials.gov)
    P1/2, N=120, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2027 --> Mar 2029 | Trial primary completion date: Mar 2026 --> Mar 2028
    Trial completion date • Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation
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    berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)
    19d
    Genomic Features and Response to Poly(ADP-ribose) Polymerase Inhibition in Metastatic Castration-Resistant Prostate Cancer. (PubMed, JCO Precis Oncol)
    Most PARPi responders had alterations in HRR genes, particularly BRCA2, although some responders lacked known biomarkers associated with PARPi response. Our findings in this real-world data set support HRR gene testing for PARPi use in mCRPC and highlight the need for novel genome-wide biomarkers for patient selection.
    Observational data • Retrospective data • Journal • BRCA Biomarker • PARP Biomarker
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    BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • BARD1 (BRCA1 Associated RING Domain 1)
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    BRCA2 mutation • BRCA mutation
    21d
    Discovery of a Selective and Potent Inhibitor of Cyclin-Dependent Kinase 12/13 Employing a Noncovalent Mechanism. (PubMed, ACS Med Chem Lett)
    In this study, we reported the design and development of a series of highly selective noncovalent inhibitors targeting CDK12 and 13. This campaign led to the identification of a lead compound exhibiting outstanding potency and favorable absorption, distribution, metabolism, and excretion profiles, as well as favorable pharmacokinetic properties, thereby demonstrating significant potential for therapeutic applications.
    Journal
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    CDK12 (Cyclin dependent kinase 12) • CDK13 (Cyclin Dependent Kinase 13)
    25d
    Comparison of the Efficacy of 35 Anticancer Drugs According to Genomic Profiling and Biological Characteristics of 14 Gastric Cancer Cell Lines. (PubMed, Int J Mol Sci)
    This study provides a framework for selecting cell lines that are responsive to each of the 35 anticancer drugs and elucidating their underlying therapeutic mechanisms through follow-up studies. Ultimately, clinical studies are required to confirm the therapeutic efficacy of the selected drugs.
    Clinical • Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • FGFR2 (Fibroblast growth factor receptor 2) • CLDN18 (Claudin 18) • CDK12 (Cyclin dependent kinase 12) • CD44 (CD44 Molecule) • TGFB1 (Transforming Growth Factor Beta 1)
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    PD-L1 overexpression • HER-2 overexpression • MET overexpression • FGFR2 overexpression
    28d
    Dual-Stimuli-Responsive Nanoplatform Delivering Molecular Glue CR8 for Synergistic CDK12 Degradation and Immunomodulatory Photothermal Therapy in TNBC. (PubMed, ACS Appl Mater Interfaces)
    This combinatorial therapy fundamentally remodeled the tumor immune microenvironment, effectively reversing immunosuppression and activating a potent antitumor immune response. By integrating targeted chemotherapy, PTT, and immunotherapy through this unique synergistic axis, the ZCPc nanoplatform presents a potent paradigm for eliciting effective antitumor immune responses in TNBC.
    Journal
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    CDK12 (Cyclin dependent kinase 12)
    1m
    Everolimus in CDK12-Deficient Metastatic Colorectal Cancer (EVER-RECODE) (clinicaltrials.gov)
    P1/2, N=38, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University
    New P1/2 trial
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    MSI (Microsatellite instability) • CDK12 (Cyclin dependent kinase 12)
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    MSI-H/dMMR
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    everolimus
    1m
    CHOMP: A Study of CHeckpoint Inhibitors in Men With prOgressive Metastatic Castrate Resistant Prostate Cancer Characterized by a Mismatch Repair Deficiency or Biallelic CDK12 Inactivation (clinicaltrials.gov)
    P2, N=40, Active, not recruiting, VA Office of Research and Development | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Dec 2026
    Enrollment closed • Trial completion date • Checkpoint inhibition • Mismatch repair
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    EGFR (Epidermal growth factor receptor) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • PMS1 (PMS1 protein homolog 1)
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    MSI-H/dMMR
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    Keytruda (pembrolizumab) • abiraterone acetate
    1m
    Characterizing Longitudinal Molecular Changes in ctDNA in Patients with Metastatic Castration-resistant Prostate Cancer. (PubMed, Clin Cancer Res)
    Our study revealed dynamic shifts in genetic mutations in patients with mCRPC following ARPI, PARPi and taxanes. Furthermore, our findings highlight associations between AR alterations and clinical outcomes, emphasizing the potential for personalized treatment strategies.
    Journal • Tumor mutational burden • BRCA Biomarker • PARP Biomarker • Circulating tumor DNA
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    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12)