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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
    1d
    Abemaciclib With or Without Atezolizumab for mCRPC (clinicaltrials.gov)
    P2, N=19, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Apr 2026 --> Nov 2025
    Trial completion • Trial completion date
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    CDK12 (Cyclin dependent kinase 12)
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    CDK12 mutation
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    Tecentriq (atezolizumab) • Verzenio (abemaciclib)
    2d
    Prevalence of homologous recombination repair genes alterations in metastatic castration-resistant prostate cancer, a multicentric study. (PubMed, Fr J Urol)
    In this study, testing contributivity was similar or higher that of other studies in the literature, and observed mutations prevalences were similar to that of other screenings of western populations. Harmonising per-centres protocols and enhancing molecular testing contributivity with the screening of circulating DNA samples and expanding its range by including non-BRCA HRR-related genes in all reference centres will enable more patients to be accurately treated by targeted therapies.
    Journal • BRCA Biomarker • PARP Biomarker
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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)
    7d
    Avelumab and M6620 for the Treatment of DDR Deficient Metastatic or Unresectable Solid Tumors (clinicaltrials.gov)
    P1/2, N=23, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Jan 2027
    Trial completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CD4 (CD4 Molecule) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
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    Bavencio (avelumab) • berzosertib (M6620)
    7d
    Potentiating mild photothermal therapy via CDK12/13-mediated AKT suppression to orchestrate ferroptosis-apoptosis crosstalk for vaccine-like immunity. (PubMed, Inflamm Res)
    These findings demonstrate that orchestrating ferroptosis-apoptosis crosstalk effectively reprograms the immune microenvironment. By repositioning MPTT from a local thermal tool to a driver of antitumor inflammation, this study establishes a mechanism-based framework for treating immunologically cold solid tumors.
    Journal
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    CD8 (cluster of differentiation 8) • CDK12 (Cyclin dependent kinase 12) • TGFB1 (Transforming Growth Factor Beta 1)
    8d
    CDK10 loss primes tumor cells for transcriptional vulnerability and sensitizes to CDK12/13 inhibition. (PubMed, Cell Death Dis)
    A genome-wide CRISPR-Cas9 screen across six breast and ovarian cancer models reveals CDK10 loss as a top-ranked enhancer of response to the selective CDK12/13 inhibitor CTX-439...These findings indicate CDK10 as a probable biomarker for patient stratification and as a co-target to boost the efficacy of transcriptional therapies. Our work reveals a previously underappreciated role for CDK10 in transcriptional resilience, emphasizing its potential to guide and enhance CDK12/13-based cancer treatments.
    Journal
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    CDK12 (Cyclin dependent kinase 12) • CDK13 (Cyclin Dependent Kinase 13)
    10d
    Meta-cancer phosphoproteomic analysis unveils association of Tau phosphosites with DNA damage response. (PubMed, Front Syst Biol)
    Additionally, the upstream kinases identified for Tau, such as CDK12/13/14/16, GSK3B, RPS6KA3, and CSNK1E, are involved in DNA damage response and carcinogenesis. These results provide a phosphosite-centric view of Tau regulation and its signalling networks in cancer, underscoring the relevance of Tau phosphosites beyond neuronal biology.
    Journal
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    CDK12 (Cyclin dependent kinase 12) • GSK3B (Glycogen Synthase Kinase 3 Beta) • MAPT (Microtubule Associated Protein Tau) • RPS6KA3 (Ribosomal Protein S6 Kinase A3)
    16d
    KEYNOTE-F86: A Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=216, Active, not recruiting, IDEAYA Biosciences | Recruiting --> Active, not recruiting
    Enrollment closed
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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) • 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) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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    HRD
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    Keytruda (pembrolizumab) • IDE161
    22d
    Centralized Homologous Recombination Repair Testing in Metastatic Castration-Resistant Prostate Cancer: Real-World Data from a Multicenter Spanish Precision Oncology Program. (PubMed, Cancers (Basel))
    Centralized HRR testing in mCRPC patients in Spain was feasible, efficient and reliable, identifying pathogenic alterations in 18% of the cases, similarly to the prevalence described in the literature. This testing approach facilitates precision medicine by improving the detection of actionable HRR alterations.
    Journal • Real-world evidence • BRCA Biomarker • PARP Biomarker
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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) • CHEK2 (Checkpoint kinase 2)
    22d
    Inhibition of RNA polymerase II-activating CDK9 and CDK12/13, but not of cell cycle relevant CDKs, induces apoptosis by downregulating the short-lived Bcl-2 proteins Mcl1 and Bfl1/A1. (PubMed, Cell Death Dis)
    Only inhibition of CDK9 (by AZD4573 and atuveciclib) or of CDK12/13 (by SR4835 and THZ531)-which target the transcriptional elongation of RNA polymerase II (RNAPII)-exerted a strong apoptotic potential. Because Bcl-2 only inhibits Bax, but not Bak, AZD4573 and SR4835 were able to induce apoptosis in Jurkat cells overexpressing Bcl-2. As tumor cells frequently upregulate Bcl-2, inhibitors of CDK9 and CDK12/13 represent promising anticancer drugs.
    Journal • IO biomarker
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    BCL2 (B-cell CLL/lymphoma 2) • MCL1 (Myeloid cell leukemia 1) • CDK4 (Cyclin-dependent kinase 4) • BCL2L1 (BCL2-like 1) • CDK12 (Cyclin dependent kinase 12) • CDK7 (Cyclin Dependent Kinase 7) • CDK9 (Cyclin Dependent Kinase 9) • CDK1 (Cyclin-dependent kinase 1) • CDC73 (Cell Division Cycle 73)
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    zemirciclib (AZD4573) • atuveciclib (BAY 1143572)
    1m
    Dual inhibition of PARP and ATR induces synthetic lethal vulnerability in prostate cancer with CDK12 deficiency. (PubMed, Mol Cancer Ther)
    In patient-derived xenograft models harboring CDK12 alterations, combined PARP and ATR inhibition led to enhanced DSB accumulation and selectively suppressed tumor growth in CDK12-defective models. These findings highlight the importance of interrogating individual genes within the HRR pathway to define distinct mechanistic vulnerabilities and provide a strong rationale for combined PARP and ATR inhibition as a novel therapeutic strategy for patients with CDK12-altered prostate cancer.
    Journal
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    HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12)
    1m
    Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
    P2, N=51, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2026 --> May 2027
    Trial completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • 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) • 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
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    Lynparza (olaparib)
    1m
    Efficacy of olaparib in advanced cancers with somatic or germline mutations in BAP1, BARD1, BRIP1 and PALB2. (PubMed, ESMO Open)
    Olaparib demonstrated meaningful clinical activity across different cancer types with somatic or germline mutations in BAP1, BARD1, BRIP1 and PALB2.
    Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • 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) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD21 (RAD21 Cohesin Complex Component) • DDR2 (Discoidin domain receptor 2) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • RAD52 (RAD52 Homolog DNA Repair Protein) • FANCE (FA Complementation Group E) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
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    BRCA2 mutation • BRCA1 mutation • HRD • ARID1A mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation • CHEK1 mutation
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    Lynparza (olaparib)