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    BIOMARKER:

    CDK12 amplification

    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
    Entrez ID:
    51755
    Related biomarkers:
    Mutation
    CNA
    3ms
    ERBB2-amplified lobular breast carcinoma exhibits concomitant CDK12 co-amplification associated with poor prognostic features. (PubMed, J Pathol Clin Res)
    ERBB2-amplified ILBC is a distinct molecular subgroup with frequent coamplification of CDK12, whereas ERBB2 sequence mutations occur only in ERBB2-unamplified ILBC. CDK12/ERBB2 co-amplification may explain the poor prognosis and therapy resistance of ERBB2-amplified ILBC.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • CDK12 (Cyclin dependent kinase 12) • CDH1 (Cadherin 1) • SOX10 (SRY-Box 10)
    |
    HER-2 positive • HER-2 overexpression • HER-2 amplification • HER-2 negative • HR negative • CDK12 mutation • CDH1 mutation • CDK12 amplification
    4ms
    Fertility-Sparing Surgery and Adjuvant Chemotherapy with Trastuzumab Result in Complete Remission in a Young Woman with Rare Primary Mucinous Ovarian Cancer due to ERBB2 Co-amplification with CDK12 and Chromosome 11q13.3 Amplicon: A Case Report and Literature Review. (PubMed, Reprod Sci)
    Treatment with fertility-sparing surgery and adjuvant chemotherapy with trastuzumab results in complete remission. This novel strategy utilizing precise diagnostics and characterization of the histo-type of rare tumors allowed personalized targeting with optimum drug response for women who yearn fertility preservation and remission from the disease, especially when there is very limited clinical experience on management of such rare ovarian tumors.
    Review • Journal • Surgery
    |
    HER-2 (Human epidermal growth factor receptor 2) • CDK12 (Cyclin dependent kinase 12)
    |
    HER-2 amplification • CDK12 amplification
    |
    Herceptin (trastuzumab)
    9ms
    Genomic Characterization of Aggressive Breast Cancer in Younger Women. (PubMed, Ann Surg Oncol)
    BCs in young women are associated with shorter survival and more aggressive genomic features, including mutations in TP53 and BRCA1, and amplifications in ERBB2 and CDK12. These findings have the potential to impact clinical trial design and treatment.
    Journal • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • CDK12 (Cyclin dependent kinase 12) • KMT2C (Lysine Methyltransferase 2C) • CDH1 (Cadherin 1) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D)
    |
    TP53 mutation • BRCA1 mutation • HER-2 amplification • PIK3CA mutation • CDK12 mutation • CDH1 mutation • CDK12 amplification
    1year
    Development, validation, and evaluation of a deep learning model to screen cyclin-dependent kinase 12 inhibitors in cancers. (PubMed, Eur J Med Chem)
    Additionally, we disclose five novel CDK12 inhibitors. These results may accelerate the discovery of novel chemical-class drugs for cancer treatment.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • CDK12 (Cyclin dependent kinase 12)
    |
    HER-2 positive • HER-2 amplification • CDK12 amplification
    2years
    A pancancer analysis of CDK12 alterations in Chinese population. (ASCO 2022)
    Genomic alterations in CDK12 are widespread among Chinese patients, with alteration rates and alteration types varying by cancer type. We identified prostate cancer as the cancer type with the highest prevalence of CDK12 oncogenic alterations. Additional analyses are ongoing.
    Clinical • Tumor Mutational Burden • Pan tumor
    |
    TMB (Tumor Mutational Burden) • CDK12 (Cyclin dependent kinase 12)
    |
    CDK12 mutation • CDK12 amplification
    2years
    Exploratory biomarker analysis from neoadjuvant atezolizumab, pertuzumab, trastuzumab plus docetaxel (NEO-PATH) in HER2+ early breast cancer (ESMO-BC 2022)
    In patients with non-pCR, LRP1B (FDR=4.04e-04), ESR1 (FDR=1.07e-4) and RAD21 (FDR=2.05e-03) were highly expressed and ESR1, luminal and MYC related genesets showed higher expression (FDR<0.05).Conclusions Luminal subtype and MYC amplification were associated with non-pCR in patients with HER2-positive EBC who were treated with immunotherapy and anti-HER2 treatment combination. Further evaluation of the predictive role of these mutations are warranted.
    Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • LRP1B (LDL Receptor Related Protein 1B) • CDK12 (Cyclin dependent kinase 12) • RAD21 (RAD21 Cohesin Complex Component)
    |
    HER-2 positive • HER-2 amplification • MYC amplification • CDK12 mutation • MYC expression • CDK12 amplification • RAD21 amplification
    |
    FoundationOne® CDx
    |
    Herceptin (trastuzumab) • Tecentriq (atezolizumab) • docetaxel • Perjeta (pertuzumab)
    2years
    Molecular characterization of gallbladder cancer (AACR 2022)
    "This large-scale genomic analysis reveals recurrent genomic events potentially associated with prognosis in GBC, including single nucleotide variants in ERBB2, KMT2C, and KMT2D, in addition to CNAs in chromosome 12q13-15 and 17q12 regions. This effort will continue to include a detailed analysis of recurrent structural variants, loss of heterozygosity loci, and analysis of the microbiota in this GBC cohort."
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • MDM2 (E3 ubiquitin protein ligase) • PBRM1 (Polybromo 1) • KMT2D (Lysine Methyltransferase 2D) • CDK4 (Cyclin-dependent kinase 4) • CDK12 (Cyclin dependent kinase 12) • SMAD4 (SMAD family member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • KMT2C (Lysine Methyltransferase 2C)
    |
    TP53 mutation • KRAS mutation • HER-2 amplification • PIK3CA mutation • ARID1A mutation • CDKN2A deletion • CCNE1 amplification • KMT2D mutation • PBRM1 mutation • CDK12 mutation • SMAD4 mutation • CDK12 amplification
    |
    MSK-IMPACT
    2years
    Dissecting the molecular mechanism of trastuzumab resistance in stage IV HER2-positive gastric cancer patients (AACR 2022)
    Overall, our results show that comparisons of samples obtained before treatment and at PD can give insight about innate and acquired resistance mechanisms to trastuzumab in stage IV, HER2-positive GC patients.
    Clinical
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCNE1 (Cyclin E1) • MCL1 (Myeloid cell leukemia 1) • CDK12 (Cyclin dependent kinase 12) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • MECOM (MDS1 And EVI1 Complex Locus)
    |
    HER-2 positive • TP53 mutation • HER-2 amplification • MYC amplification • CDKN2A deletion • CCNE1 amplification • MCL1 amplification • CDK12 amplification • TP53 amplification
    |
    Herceptin (trastuzumab)
    over2years
    First-in-human HER2-targeted Bispecific Antibody KN026 for the Treatment of Patients with HER2-positive Metastatic Breast Cancer: Results from a Phase I Study. (PubMed, Clin Cancer Res)
    KN026, a HER2 bispecific antibody, was well tolerated and achieved comparable efficacy as trastuzumab and pertuzumab doublet even in the more heavily pretreated patients. Co-amplification of HER2/CDK12 may define patients who benefit more from KN026.
    Clinical • P1 data • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • CDK12 (Cyclin dependent kinase 12)
    |
    HER-2 positive • HER-2 amplification • CDK12 amplification
    |
    Herceptin (trastuzumab) • Perjeta (pertuzumab) • anbenitamab (KN026)
    over2years
    First-in-human HER2-targeted bispecific antibody KN026 for the treatment of patients with HER2-positive metastatic breast cancer: Results from a phase I study (SABCS 2021)
    CONCLUSION KN026, a HER2 bispecific antibody, is well tolerated, with a favorable safety profile and promising anti-tumor activity in the context of its class in patients with HER2-positive breast cancer. Co-amplification of HER2/CDK12 may define patients who benefit more from KN026.
    Clinical • P1 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • CDK12 (Cyclin dependent kinase 12)
    |
    HER-2 positive • HER-2 amplification • CDK12 amplification
    |
    anbenitamab (KN026)