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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
    1m
    A novel classification of small bowel adenocarcinoma based on the hidden genome classifier: a multi-institutional study. (PubMed, J Natl Cancer Inst)
    SBAs display genomic heterogeneity. The novel HGC stratifies these tumors based on homology to foregut or hindgut alterations and may be superior to anatomic location for characterizing pathology. Additional studies are needed to validate and further explore these findings.
    Clinical • Journal
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ARID1A (AT-rich interaction domain 1A) • CDK12 (Cyclin dependent kinase 12) • APC (APC Regulator Of WNT Signaling Pathway)
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    TP53 mutation • KRAS mutation • ARID1A mutation
    1m
    Inhibition of cyclin-dependent kinases 12/13 using CT7439 as a treatment for colorectal cancer with CDK12 upregulation. (PubMed, Mol Oncol)
    We tested the efficacy of CT7439, a novel CDK12/13 inhibitor and cyclin K degrader, which showed cytotoxicity in the low nanomolar range, reduced BRCA1 expression, and concomitant DNA damage. Together, our data support further clinical development of CDK12/13 inhibition in CRC.
    Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • CDK12 (Cyclin dependent kinase 12) • CDK13 (Cyclin Dependent Kinase 13)
    1m
    Aryl Aldehyde-Anchored Small Molecules Recruit FBXO22 for Targeted Degradation of NSD2. (PubMed, J Med Chem)
    Mechanistic investigations confirmed that degradation is dependent on FBXO22, the ubiquitin-proteasome system, and the neddylation pathway, with mutagenesis identifying Cys326 as the critical residue for covalent engagement. This work establishes a stable covalent ligand for FBXO22, expanding chemical space of PROTAC design by introducing an accessible aldehyde-based E3 ligase ligand with broad potential for protein degradation.
    Journal
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    CDK12 (Cyclin dependent kinase 12) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
    2ms
    Molecular Glues Recruiting RNF213 As an E3 Ligase for Targeted Protein Degradation: A Minimal Dibromoacetamide Warhead As a Recruitment Ligand. (PubMed, J Am Chem Soc)
    We developed CYB-5067 by equipping the pan-FGFR inhibitor Infigratinib with a minimal dibromoacetamide covalent warhead...Our work identifies RNF213 as an exploitable ligase for TPD and establishes covalent molecular glues as a modular platform. This strategy expands the scope of degrader design beyond conventional E3 ligases, offering an avenue for developing potent and selective therapeutics.
    Journal
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    FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • CDK12 (Cyclin dependent kinase 12) • CRBN (Cereblon)
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    Truseltiq (infigratinib)
    2ms
    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)
    2ms
    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)
    2ms
    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)
    2ms
    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)
    2ms
    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)
    2ms
    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)
    2ms
    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
    2ms
    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)