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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
    Dynamics of Postmortem Gene Expression in Normal and Neoplastic Murine Liver. (PubMed, Life (Basel))
    This pattern developed despite formally adequate RNA quality (RQN) and the absence of clear signs of progressive autolysis in histology, indicating the insufficiency of standard quality criteria for detecting postmortem changes. These findings collectively underscore the critical importance of minimizing and controlling PMI during the biobanking of oncological samples for reliable transcriptomic research.
    Preclinical • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)
    9d
    CX-5461-04: Study of CX-5461 in Patients With Solid Tumours and BRCA1/2, PALB2 or Homologous Recombination Deficiency (HRD) Mutation (clinicaltrials.gov)
    P1, N=52, Recruiting, Senhwa Biosciences, Inc. | Trial completion date: Dec 2026 --> Mar 2027 | Trial primary completion date: Dec 2025 --> Mar 2027
    Trial completion date • Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CCNE1 (Cyclin E1) • KMT2D (Lysine Methyltransferase 2D) • CDK12 (Cyclin dependent kinase 12) • KMT2C (Lysine Methyltransferase 2C) • SLFN11 (Schlafen Family Member 11) • CHEK2 (Checkpoint kinase 2) • CREBBP (CREB binding protein) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • RBBP8 (RB Binding Protein 8, Endonuclease) • XRCC2 (X-Ray Repair Cross Complementing 2) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • MAD2L2 (Mitotic Arrest Deficient 2 Like 2) • CDC25C (Cell Division Cycle 25C) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • MUS81 (MUS81 Structure-Specific Endonuclease Subunit) • CDC25A (Cell Division Cycle 25A) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1) • RAD17 (RAD17 Checkpoint Clamp Loader Component) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
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    BRCA2 mutation • BRCA1 mutation • PALB2 mutation
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    pidnarulex (CX-5461)
    13d
    Characteristics and therapeutic resistance mechanisms of the prostate cancer immune microenvironment: a comprehensive analysis from bench to clinic. (PubMed, Front Pharmacol)
    Overcoming resistance will require an integrated strategy combining high-resolution spatial multi-omics, advanced disease models, and biomarker-driven trials focused on rational combinations that co-target the AR pathway. Prioritizing this mechanistic approach is therefore critical to advance precision therapy for prostate cancer.
    Review • Journal • PARP Biomarker • IO biomarker
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    CD8 (cluster of differentiation 8) • CDK12 (Cyclin dependent kinase 12)
    15d
    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=35, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=120 --> 35
    Enrollment closed • Enrollment change
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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)
    16d
    Genetic mutations in salivary duct carcinoma. (PubMed, Otolaryngol Pol)
    <br><br><b></b> This study delineated the mutational spectrum of recurrent and/or metastatic SDC. Even in advanced disease, prognostically relevant mutations were identified, emphasizing the clinical importance of cancer genomic profiling tests.
    Journal • BRCA Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • CDK12 (Cyclin dependent kinase 12) • NOTCH3 (Notch Receptor 3)
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    TP53 mutation
    26d
    Phosphosite-centric regulatory network of ATAD2 and its involvement in transcriptional networks. (PubMed, Mol Genet Genomics)
    In contrast, phosphorylation at S337 and T1152 correlated with proteins involved in transcriptional repression, indicating its involvement in inhibitory function. Collectively, these findings indicate the involvement of the ATAD2 phosphoregulatory network in transcriptional regulation and provide insights into the regulatory landscape of ATAD2, laying the groundwork for its potential therapeutic targeting in cancers.
    Journal
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    CDK12 (Cyclin dependent kinase 12) • CDK13 (Cyclin Dependent Kinase 13)
    1m
    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
    1m
    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
    1m
    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)
    1m
    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)
    1m
    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)
    2ms
    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