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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
    7d
    Precision Medicine in Prostate Cancer with a Focus on Emerging Therapeutic Strategies. (PubMed, Biomedicines)
    Integrating multi-omics technologies, liquid biopsy platforms, and AI-assisted imaging offers new opportunities for dynamic disease monitoring and biology-driven treatment selection. By consolidating current clinical practices with emerging experimental directions, this review provides clinicians and researchers with a comprehensive perspective on the evolving landscape of precision medicine in prostate cancer and highlights future opportunities to improve patient outcomes.
    Review • Journal • BRCA Biomarker • MSi-H Biomarker • PARP Biomarker • IO biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • SPOP (Speckle Type BTB/POZ Protein)
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    MSI-H/dMMR • ATM mutation
    11d
    PEPN2112: Elimusertib for the Treatment of Relapsed or Refractory Solid Tumors (clinicaltrials.gov)
    P1/2, N=31, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2025 --> Mar 2026
    Trial completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • POLD1 (DNA Polymerase Delta 1) • FOXO1 (Forkhead box O1) • XRCC2 (X-Ray Repair Cross Complementing 2) • ATF1 (Activating Transcription Factor 1) • PAX3 (Paired Box 3)
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    elimusertib (BAY 1895344)
    11d
    NePtune: Study of Neoadjuvant PARP Inhibition Followed by Radical Prostatectomy in Patients With Unfavorable Intermediate-Risk or High-Risk Prostate Cancer With Select HRR Gene Alterations (clinicaltrials.gov)
    P2, N=32, Recruiting, Rana McKay, MD | Trial primary completion date: Dec 2025 --> Mar 2026
    Trial primary completion date
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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) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L2 (RAD54 Like 2)
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    Lynparza (olaparib) • triptorelin • goserelin acetate • leuprolide acetate for depot suspension
    12d
    Nivolumab + Docetaxel + ADT in mHSPC Patients With DDRD or Inflamed Tumors (clinicaltrials.gov)
    P2, N=60, Active, not recruiting, Xiao X. Wei, MD | Trial completion date: Dec 2025 --> Jun 2026
    Trial completion date
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    PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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    PD-L1 expression • MSI-H/dMMR
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    OncoPanel™ Assay
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    Opdivo (nivolumab) • docetaxel • goserelin acetate • Firmagon (degarelix) • leuprolide acetate for depot suspension
    13d
    Cervical HPV-independent adenosquamous carcinoma: report of a case series. (PubMed, Virchows Arch)
    The tumours were advanced stage at diagnosis: stage IIB (1 case), IIIC1 (2 cases), and IVB (2 cases). Our findings suggest that cervical adenosquamous carcinoma should be classified into HPV-associated and HPV-independent types and this should be reflected in updated WHO Classifications.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDK12 (Cyclin dependent kinase 12) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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    CDKN2A deletion
    18d
    Therapeutic targeting of CDK12: a medicinal chemistry perspective. (PubMed, Bioorg Med Chem)
    This paper provides a detailed review of various types of CDK12 small-molecule inhibitors/degraders, primarily based on key structural frameworks. It focuses on exploring the existing structure-activity relationships, aiming to offer a comprehensive perspective for developing highly selective CDK12-targeted inhibitors/degraders and providing valuable insights for future novel drug development.
    Review • Journal
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    CDK12 (Cyclin dependent kinase 12)
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    CDK12 mutation
    20d
    Structure-Activity and Structure-Degradation Relationship Studies of 2-Amino-6-(benzimidazol-2-ylmethyl)-N9-heteroarylpurines as Potent and Selective CDK12/13 Inhibitors and Cyclin K Degraders. (PubMed, J Med Chem)
    In vitro target engagement and in vivo PK/PD studies in mice demonstrate dose-dependent CycK degradation that closely tracks systemic compound exposure. These findings establish CycK as a suitable proximal PD biomarker for this inhibitor class and highlight purine-based scaffolds as a rational framework for the development of bifunctional CDK12/CycK inhibitors and degraders.
    Journal
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    CDK12 (Cyclin dependent kinase 12)
    21d
    Assessing the association between homologous recombination deficiency scores and treatment response in localized and metastatic prostate cancer. (PubMed, J Pathol Clin Res)
    Molecular characterization showed that higher homologous recombination deficiency scores were associated with higher alteration rates in genes such as BRCA2, CDK12, MYC, and PTEN. This study reveals that higher homologous recombination deficiency scores are associated with unfavorable treatment efficacy of radical prostatectomy in localized prostate cancer and of androgen receptor target inhibitor treatment in metastatic prostate cancer.
    Journal
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    BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12)
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    HRD
    26d
    Targeted next-generation sequencing reveals genomic differences between male and female breast cancer. (PubMed, Transl Cancer Res)
    We concluded that MBC and FBC exhibit both genomic similarities and distinctions in our study. In the context of precision medicine, this study may provide new ideas and a basis for the diagnosis and treatment of MBC.
    Journal • Next-generation sequencing • Tumor mutational burden
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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) • TMB (Tumor Mutational Burden) • CDK12 (Cyclin dependent kinase 12) • KMT2C (Lysine Methyltransferase 2C) • GATA3 (GATA binding protein 3)
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    TP53 mutation • PIK3CA mutation • CDK12 mutation
    28d
    INSPIRE: Ipilimumab With Nivolumab for Molecular-selected Patients With Castration-resistant Prostate Cancer (clinicaltrials.gov)
    P2, N=69, Completed, Radboud University Medical Center | Active, not recruiting --> Completed
    Trial completion
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    TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset)
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    TMB-H
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    Opdivo (nivolumab) • Yervoy (ipilimumab)