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    BIOMARKER:

    CCNE1 overexpression

    i
    Other names: CCNE1, CCNE, Cyclin E1
    Entrez ID:
    898
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    9d
    The Clinicopathological Significance of the Cyclin D1/E1-Cyclin-Dependent Kinase (CDK2/4/6)-Retinoblastoma (RB1/pRB1) Pathway in Epithelial Ovarian Cancers. (PubMed, Int J Mol Sci)
    Our data not only identified the prognostic/predictive significance of these key cell cycle regulators but also demonstrate the importance of sub-cellular localisation. CDK2 targeting in cyclin-E1-amplified OCs could be a rational approach.
    Journal
    |
    RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • CDK2 (Cyclin-dependent kinase 2)
    |
    CCNE1 amplification • CCNE1 overexpression • CCND1 expression • CCND1 expression + CDK4 expression • CCNE1 expression
    10d
    RAD52-dependent mitotic DNA synthesis is required for genome stability in Cyclin E1-overexpressing cells. (PubMed, Cell Rep)
    Finally, analysis of breast cancer samples reveals a positive correlation between Cyclin E1 amplification and RAD52 expression. These findings demonstrate the importance of suppressing mitotic defects in Cyclin E1-overexpressing cells through RAD52.
    Journal
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    CCNE1 (Cyclin E1) • RAD52 (RAD52 Homolog DNA Repair Protein)
    |
    CCNE1 amplification • CCNE1 overexpression
    19d
    CircROR1 upregulates CCNE1 expression to promote melanoma invasion and metastasis by recruiting KAT2A. (PubMed, Exp Dermatol)
    CircROR1 upregulates CCNE1 expression through KAT2A-mediated histone acetylation. Our research confirms the critical role of CircROR1 in melanoma invasion and metastasis, and CircROR1 could serve as a potential therapeutic target for melanoma treatment.
    Journal
    |
    CCNE1 (Cyclin E1) • TIMP2 (TIMP Metallopeptidase Inhibitor 2) • MMP9 (Matrix metallopeptidase 9)
    |
    CCNE1 overexpression • CCNE1 expression
    2ms
    ceRNA Network and WGCNA Analyses of Differentially Expressed Genes in Cervical Cancer Tissues for Association with Survival of Patients. (PubMed, Reprod Sci)
    The ceRNA network and WGCNA analyses are useful to identify novel DEGs that can serve as prognostic markers in cervical cancer. The DEGs will be validated in future studies.
    Journal
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    CCNE1 (Cyclin E1) • LIFR (LIF Receptor Subunit Alpha) • CCNB1 (Cyclin B1) • E2F1 (E2F transcription factor 1)
    |
    CCNE1 overexpression
    2ms
    Cyclin-Dependent Kinase 2 (CDK2) Inhibitors and others novel CDK Inhibitors (CDKi) in Breast Cancer: Clinical Trials, Current Impact, and Future Directions. (PubMed, Crit Rev Oncol Hematol)
    The review extends beyond CDK2i to encompass novel emerging CDK4 inhibitors, combined CDK2/4/6 inhibitors, and the well-known pan-CDK inhibitors including those specifically directed at CDK2. Delving into the results, we critically appraise the observed clinical efficacy and offer valuable insights into their potential impact and future applications.
    Review • Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CCNE1 (Cyclin E1)
    |
    MYC overexpression • CCNE1 overexpression • MYC expression
    2ms
    Regulation and tumor-suppressive function of the miR-379/miR-656 (C14MC) cluster in cervical cancer. (PubMed, Mol Oncol)
    Thus, C14MC is a tumor-suppressive and methylation-regulated miRNA cluster in CC. Reactivation of C14MC can be useful in the management of CC.
    Journal
    |
    CCNE1 (Cyclin E1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • MIR494 (MicroRNA 494)
    |
    MYC overexpression • CCNE1 overexpression • CDKN1B expression
    3ms
    Discovery of Novel Antitumor Small-Molecule Agent with Dual Action of CDK2/p-RB and MDM2/p53. (PubMed, Molecules)
    The results of the druggability evaluation showed that III-13 was characterized by low bioavailability and poor membrane permeability when orally administered, suggesting the necessity of further structural modifications. Therefore, this study provided a lead compound for antitumor drugs, especially those against CCNE1-amplified tumor proliferation.
    Journal
    |
    CCNE1 (Cyclin E1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • CDK2 (Cyclin-dependent kinase 2)
    |
    CCNE1 amplification • CCNE1 overexpression
    6ms
    FBXL12 degrades FANCD2 to regulate replication recovery and promote cancer cell survival under conditions of replication stress. (PubMed, Mol Cell)
    Finally, depletion of FBXL12 exacerbated oncogene-induced replication stress and sensitized cancer cells to drug-induced replication stress by WEE1 inhibition. Collectively, our results indicate that FBXL12 constitutes a vulnerability and a potential therapeutic target in CYCLIN E-overexpressing cancers.
    Journal
    |
    CHEK1 (Checkpoint kinase 1) • FANCD2 (FA Complementation Group D2)
    |
    CCNE1 overexpression
    8ms
    Overexpression of BQ323636.1 contributes to anastrozole resistance in AR+ve/ER+ve breast cancer. (PubMed, J Pathol)
    BQ overexpression reverses the effect of anastrozole in ER+ve breast cancer in an AR-dependent manner, whilst co-treatment with the AR antagonist bicalutamide recovered its therapeutic effect both in vitro and in vivo.
    Journal
    |
    ER (Estrogen receptor) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • NCOR2 (Nuclear Receptor Corepressor 2) • CDK2 (Cyclin-dependent kinase 2)
    |
    ER positive • CCNE1 overexpression • AR expression • CCNE1 expression • CDK2 expression
    |
    anastrozole • bicalutamide
    8ms
    PKMYT1: A Potential Target for CCNE1 Amplificated Colorectal Tumors. (PubMed, Cell Biochem Biophys)
    In CCNE1 amplificated colorectal tumor cells, knockdown of PKMYT1 reduced cells in S phase, inhibited cell proliferation and promoted cell apoptosis, confirming that PKMYT1 was a potential therapeutic target for colorectal tumor. This study may verify a potential therapeutic target and provide a new idea for the treatment of colorectal cancer in the future.
    Journal
    |
    CCNE1 (Cyclin E1) • CDK1 (Cyclin-dependent kinase 1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    CCNE1 amplification • CCNE1 overexpression • CCNE1 expression
    8ms
    OVEREXPRESSION OF CYCLIN DEPENDENT KINASES AND CYCLINS ACROSS SARCOMAS BEYOND CDK4 (CTOS 2023)
    We identified overexpressers of CDK and cyclin genes among a heterogeneous sample of sarcoma patients. By setting a threshold of 2 SD above the mean of each gene we captured the top ~2% of expressers, and by considering subtypes with ≥ 25% of cases above that threshold we accurately identified known associations between CDK4/LPS and CCND1/Ewing sarcoma while also revealing new associations. The most notable overexpressers were chordoma (CDK7, CDK18), CCS (CDK2, CCNA1), RCS (CCND2), and RMS (CDK6, CDK8, CCND2, CCNE1).
    CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • CCND2 (Cyclin D2) • CDK2 (Cyclin-dependent kinase 2) • CDK7 (Cyclin Dependent Kinase 7) • CDK9 (Cyclin Dependent Kinase 9) • CCNA1 (Cyclin A1)
    |
    CCNE1 overexpression • CDK4 amplification • CCND1 overexpression • CDK4 overexpression • CDK2 overexpression • CDK6 overexpression • CCND2 overexpression • PPP3CA expression
    |
    MI Tumor Seek™
    10ms
    IGNITE: A PHASE II SIGNAL-SEEKING TRIAL OF ADAVOSERTIB TARGETING RECURRENT HIGH GRADE SEROUS OVARIAN CANCER WITH CYCLIN E1 OVER-EXPRESSION WITH AND WITHOUT GENE AMPLIFICATION (IGCS 2023)
    No abstract available
    P2 data
    |
    CCNE1 (Cyclin E1)
    |
    CCNE1 overexpression
    |
    adavosertib (AZD1775)
    10ms
    BLM overexpression as a predictive biomarker for CHK1 inhibitor response in PARP inhibitor-resistant BRCA-mutant ovarian cancer. (PubMed, Sci Transl Med)
    Using high-throughput drug screens, we identified ataxia telangiectasia and rad3-related protein/checkpoint kinase 1 (CHK1) pathway inhibitors as cytotoxic and further validated the activity of the CHK1 inhibitor (CHK1i) prexasertib in PARPi-sensitive and -resistant BRCA-mutant HGSC cells and xenograft mouse models...BRCA reversion mutation in previously PARPi-treated BRCA-mutant patients was not associated with resistance to CHK1i. Our findings suggest that replication fork-related genes should be further evaluated as biomarkers for CHK1i sensitivity in patients with BRCA-mutant HGSC.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    CCNE1 (Cyclin E1) • BRCA (Breast cancer early onset) • ATR (Ataxia telangiectasia and Rad3-related protein) • BLM (BLM RecQ Like Helicase)
    |
    CCNE1 overexpression • BRCA mutation
    |
    prexasertib (ACR-368)
    10ms
    Long noncoding RNA LINC02568 sequesters microRNA-874-3p to facilitate malignancy in breast cancer cells via cyclin E1 overexpression. (PubMed, Oncol Res)
    In conclusion, the tumor-promoting functions of LINC02568 in breast cancer cells were enhanced by sequestering miR-874-3p and consequently over-expressing CCNE1. Our data may facilitate the identification of novel therapeutic targets in clinical settings.
    Journal
    |
    CCNE1 (Cyclin E1)
    |
    CCNE1 overexpression • CCNE1 expression
    11ms
    Adavosertib Enhances Antitumor Activity of Trastuzumab Deruxtecan in HER2-Expressing Cancers. (PubMed, Clin Cancer Res)
    We provide rationale for combining T-DXd with adavosertib in HER2-expressing cancers, especially with co-occuring CCNE1 amplifications.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • CCNE1 (Cyclin E1)
    |
    HER-2 overexpression • HER-2 amplification • HER-2 expression • CCNE1 amplification • CCNE1 overexpression • CCNE1 expression
    |
    Enhertu (fam-trastuzumab deruxtecan-nxki) • adavosertib (AZD1775)
    12ms
    Circular RNA circSEMA5A facilitates colorectal cancer development by regulating microRNA-195-5p to target CCNE1 axis. (PubMed, Cell Signal)
    To summarize, circSEMA5A is a novel circRNA that serves as an oncogene in CRC progression. CircSEMA5A facilitates CRC cell malignancy and tumor growth through sponging miR-195-5p to upregulate CCNE1, thus providing a new direction for CRC diagnosis and targeted therapy.
    Journal
    |
    CCNE1 (Cyclin E1) • SEMA5A (semaphorin 5A) • MIR195 (MicroRNA 195)
    |
    CCNE1 overexpression • CCNE1 expression
    almost1year
    Correlation of cyclin E1 expression and clinical outcomes in a phase 1b dose-escalation study of azenosertib (ZN-c3), a WEE1 inhibitor, in combination with chemotherapy (CT) in patients (pts) with platinum-resistant or refractory (R/R) epithelial ovarian, peritoneal, or fallopian tube cancer (EOC). (ASCO 2023)
    This open-label, multicenter study (NCT04516447) assessed azenosertib + paclitaxel (PAC), carboplatin (Carbo), gemcitabine (GEM), or pegylated liposomal doxorubicin (PLD) in pts with metastatic high-grade serous EOC after ≤2 lines of CT including platinum CT. Azenosertib + CT is well tolerated and has encouraging clinical activity, with durable responses in pts with platinum R/R EOC. Pts with Cyclin E1 overexpressing tumors, a subgroup with suboptimal benefits from CT, demonstrated significant improvements in ORR and PFS vs pts with tumors having low expression. These data support a planned trial of azenosertib + CT vs CT alone in Cyclin E1 overexpressing platinum R/R EOC.
    Clinical • Clinical data • P1 data • Combination therapy
    |
    CCNE1 (Cyclin E1)
    |
    CCNE1 amplification • CCNE1 overexpression • CCNE1 expression
    |
    carboplatin • gemcitabine • paclitaxel • pegylated liposomal doxorubicin • azenosertib (ZN-c3)
    1year
    CCNE1 and PLK1 mediates resistance to palbociclib in HR+/HER2- metastatic breast cancer. (PubMed, Clin Cancer Res)
    We confirm the association of non-luminal subtype and CCNE1 with resistance to CDK4/6i+ET in HR+ MBC. High levels of PLK1 mRNA identify patients with poor response to palbociclib, suggesting PLK1 could also play a role in the setting of resistance to CDK4/6i.
    Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CCNE1 (Cyclin E1) • PLK1 (Polo Like Kinase 1)
    |
    ER positive • HR positive • HER-2 negative • CCNE1 overexpression • CCNE1 expression
    |
    Ibrance (palbociclib) • capecitabine
    1year
    ATRN-119 and ATRN-W1051: Novel and potentially well tolerated ATR and WEE1 inhibitors for targeted cancer treatment (AACR 2023)
    Importantly, ATRN-W1051 exhibits low off-target inhibition of the PLK family of kinases (PLK1, PLK2 and PLK3), which are substantially inhibited by the leading WEE1i in the clinic (AZD1775 and ZN-c3)1. These preclinical data suggest that ATRN-W1051 may be a potential therapeutic candidate for CCNE1-overexpressing HGSOC. Together, ATRN-119 and ATRN-W1051 provide promising alternative DNA replication checkpoint inhibitors for the treatment of a variety of cancers.
    BRCA Biomarker • PARP Biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • CCNE1 (Cyclin E1) • PLK1 (Polo Like Kinase 1) • PLK2 (Polo Like Kinase 2)
    |
    CCNE1 amplification • CCNE1 overexpression
    |
    adavosertib (AZD1775) • azenosertib (ZN-c3) • APR-1051 • ATRN-119
    1year
    Glucose dependent CD73+ CAFs enforce a tumor metabolic barrier that promotes T cell exclusion (AACR 2023)
    Furthermore, blockade of CD73 in CD73+ CAFs decreases the expression of the glucose transporter, Glut1. All together, these data suggest that CD73 may serve as a marker of glucose dependent CAFs that alter the metabolic niche to block T cell infiltration into tumors.
    IO biomarker
    |
    CD8 (cluster of differentiation 8) • CCNE1 (Cyclin E1) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • NT5E (5'-Nucleotidase Ecto) • SLC2A1 (Solute Carrier Family 2 Member 1) • VGLL3 (Vestigial Like Family Member 3)
    |
    CCNE1 overexpression • CD73 expression
    over1year
    CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study. (PubMed, Cancer)
    This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1)
    |
    CCNE1 amplification • CCNE1 overexpression • CCNE1 elevation
    over1year
    Preclinical evaluation of CDK4 phosphorylation predicts high sensitivity of pleural mesotheliomas to CDK4/6 inhibition. (PubMed, Mol Oncol)
    We evaluated the impact of CDK4/6 inhibition by palbociclib in 28 MPM cell lines including 19 patient-derived ones, using various approaches including RNA-sequencing...Its absence in some highly proliferative MPMs was linked to very high p16 (CDKN2A) expression, which was also observed in public datasets in tumors from short survival patients. Our study supports the evaluation of CDK4/6 inhibitors for MPM treatment, in monotherapy or combination therapy.
    Preclinical • Journal
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1)
    |
    CCNE1 overexpression • RB1 overexpression
    |
    Ibrance (palbociclib)
    over1year
    CDK4/6 initiates Rb inactivation and CDK2 activity coordinates cell-cycle commitment and G1/S transition. (PubMed, Sci Rep)
    Together, our data suggest that CDK4/6 inactivates Rb to begin E2F and CDK2 activation, and high CDK2 activity is necessary and sufficient to generate a bistable switch for Rb phosphorylation before DNA replication. These findings highlight how cells initiate the cell cycle and subsequently commit to the cell cycle before the G1/S transition.
    Journal
    |
    CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • CDK2 (Cyclin-dependent kinase 2)
    |
    CCNE1 overexpression • RB1 positive
    over1year
    CDK2 inhibition with BLU-222 in combination with ribociclib demonstrates robust antitumor activity in pre-clinical models of CDK4/6 inhibitor-naïve and -resistant HR+/HER2- breast cancer (SABCS 2022)
    Finally, the activity of BLU-222 was evaluated in a patient-derived xenograft (PDX) model of CDK4/6 inhibitor-resistant HR+/HER2- breast cancer where the patient had progressed on 1L palbociclib/fulvestrant and 2L abemaciclib/fulvestrant therapy. Additionally, the improved durability of response when BLU-222 is combined with CDK4/6 inhibitors in the CDK4/6-naïve setting supports the combination of these agents as 1L treatment. BLU-222 is currently under investigation in VELA (NCT05252416), a phase 1/2, first-in-human trial for patients with cyclin E aberrant cancers and HR+/HER2- breast cancer.
    Preclinical • Combination therapy
    |
    HER-2 (Human epidermal growth factor receptor 2) • CCNE1 (Cyclin E1)
    |
    HR positive • HER-2 negative • CCNE1 overexpression • CCNE1 expression
    |
    Ibrance (palbociclib) • Verzenio (abemaciclib) • Kisqali (ribociclib) • fulvestrant
    over1year
    Clinical and genomic landscape of breast cancers carrying CCNE1 amplification (SABCS 2022)
    CCNE1 amp was also associated with numerically inferior median PFS (7.3 vs 20.8 months in CCNE1 amp [n=5] vs CCNE1 non-amp [n=106]; HR 3.1, 95% CI 1.24-7.87, p=0.01) on first line trastuzumab/pertuzumab/taxane treatment in HER2+ metastatic BCs, with a trend toward significance after adjusting for FGA and TMB (p=0.09). CCNE1 amp is associated with specific clinicopathological and genomic features in BCs and linked to an increased genomic instability. CCNE1 amp defines a subset of metastatic BCs with marked poor clinical response to available standard-of-care treatments. Further studies testing novel therapeutic approaches, including synthetic lethality-based strategies targeting CCNE1 amp and CDK2-selective inhibition, are warranted.
    Clinical • Tumor mutational burden
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CCNE1 (Cyclin E1) • CDH1 (Cadherin 1) • ARID2 (AT-Rich Interaction Domain 2)
    |
    HER-2 negative • CCNE1 amplification • CCNE1 overexpression
    |
    MSK-IMPACT
    |
    Herceptin (trastuzumab) • Perjeta (pertuzumab)
    over1year
    APPLICATION OF SHALLOW WHOLE GENOME SEQUENCING TO IDENTIFY THERAPEUTIC OPPORTUNITIES IN P53ABN ENDOMETRIAL CANCERS (IGCS 2022)
    sWGS is a relatively inexpensive tool that can be performed on FFPE, and may be used to identify opportunities for PARPi therapy, with 26% of p53abn EC identified as having HRD signatures. Opportunities for anti-HER2 therapy and targeting CCNE1 (Wee1i) were also identified, although IHC detected a significantly greater proportion of p53abn ECs overexpressing HER2 and CCNE1 compared to CN amplification calls on sWGS. This may, in part, be explained by intratumor heterogeneity.
    PARP Biomarker
    |
    HRD (Homologous Recombination Deficiency) • CCNE1 (Cyclin E1)
    |
    HER-2 overexpression • HER-2 amplification • HRD • CCNE1 amplification • CCNE1 overexpression
    over1year
    COUMERMYCIN-A1 (CA1) IDENTIFIED AS A FIRST-IN-CLASS CDC45-MCM-GINS HELICASE INHIBITOR OFFERING THERAPEUTIC POTENTIAL FOR OSTEOSARCOMA TREATMENT (CTOS 2022)
    Cells were also co-treated with CA1 or gemcitabine for 18 hours, allowed to recover for 8 hours, and then treated with the opposite treatment for another 18 hours... The discovery of these aminocoumarins as first-in-class, effective CMG inhibitor provides an starting point for translating CMG inhibition in combinations in osteosarcoma. Notably, the observed effect is seen across multiple osteosarcoma cell lines. Past work with CA1 provides supportive evidence that inhibitory levels can be administered with acceptable toxicity.
    PARP Biomarker
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • RPA2 (Replication Protein A2)
    |
    MYC overexpression • CCNE1 overexpression • MYC expression
    |
    gemcitabine
    over1year
    CCNE1 is a potential target of Metformin for tumor suppression of ovarian high-grade serous carcinoma. (PubMed, Cell Cycle)
    Furthermore, molecular simulation docking showed that Metformin may bind to CCNE1 protein, suggesting that CCNE1 could be a potential target for Metformin. Our data revealed that Metformin has antitumor effects on ovarian cancer and CCNE1 could be a potential target for Metformin.
    Journal
    |
    CCNE1 (Cyclin E1)
    |
    CCNE1 overexpression • CCNE1 expression • CCNE1 elevation
    |
    metformin
    over1year
    LncRNA STK4 antisense RNA 1 (STK4-AS1) promoted osteosarcoma by inhibiting p53 expression. (PubMed, Cancer Biomark)
    LncRNA STK4-AS1 promoted the cell cycle of osteosarcoma cells by inhibiting p53 expression.
    Journal
    |
    CCNA2 (Cyclin A2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    |
    CCNE1 overexpression • TP53 expression • TP53 overexpression
    almost2years
    C2orf40 inhibits metastasis and regulates chemo-resistance and radio-resistance of nasopharyngeal carcinoma cells by influencing cell cycle and activating the PI3K/AKT/mTOR signaling pathway. (PubMed, J Transl Med)
    The results clarified the biological functions and mechanisms of C2orf40, as a tumor suppressor gene, in NPC, and provided a potential molecular target for improving the sensitivity of NPC to radiotherapy and chemotherapy.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CCNE1 (Cyclin E1) • RAD51 (RAD51 Homolog A) • CDK1 (Cyclin-dependent kinase 1) • CDC25A (Cell Division Cycle 25A) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1)
    |
    CCNE1 overexpression • CCNE1 expression
    almost2years
    High cyclin E1 protein, but not gene amplification, is prognostic for basal-like breast cancer. (PubMed, J Pathol Clin Res)
    Overall CCNE1 gene amplification is not equivalent between BLBC and HGSOC. However, high cyclin E1 protein expression can co-occur with HR defects in both BLBC and HGSOC, and is associated with poor prognosis in BLBC.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • CCNE1 (Cyclin E1)
    |
    TP53 mutation • BRCA1 mutation • CCNE1 amplification • CCNE1 overexpression • CCNE1 expression • TP53 amplification
    almost2years
    TP53 and TP53-associated genes are correlated with the prognosis of paediatric neuroblastoma. (PubMed, BMC Genom Data)
    TP53 and TP53-associated genes CCNE1, CDK2, CHEK2 and SESN1 were significantly associated with the clinical outcomes of paediatric neuroblastoma.
    Journal
    |
    TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CHEK2 (Checkpoint kinase 2) • CDK2 (Cyclin-dependent kinase 2)
    |
    TP53 mutation • MYCN amplification • CCNE1 amplification • CCNE1 overexpression
    almost2years
    Multi-omics analyses provide novel biological insights to distinguish lobular ductal types of invasive breast cancers. (PubMed, Breast Cancer Res Treat)
    Our findings identify novel molecular candidates that potentially drive and modify the disease differentially among these histotypes.
    Journal • BRCA Biomarker
    |
    CCNE1 (Cyclin E1) • BRCA (Breast cancer early onset) • CDH1 (Cadherin 1) • PGBD5 (PiggyBac Transposable Element Derived 5) • GSTA2 (Glutathione S-Transferase Alpha 2) • BTG2 (BTG Anti-Proliferation Factor 2) • MIR195 (MicroRNA 195)
    |
    CCNE1 overexpression • CDH1 mutation
    almost2years
    CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition. (PubMed, Nature)
    To inhibit PKMYT1, we developed RP-6306, an orally bioavailable and selective inhibitor that shows single-agent activity and durable tumour regressions when combined with gemcitabine in models of CCNE1 amplification. CCNE1 overexpression disrupts CDK1 homeostasis at least in part through an early activation of the MMB-FOXM1 mitotic transcriptional program. We conclude that PKMYT1 inhibition is a promising therapeutic strategy for CCNE1-amplified cancers.
    Journal • Synthetic lethality
    |
    CCNE1 (Cyclin E1) • FOXM1 (Forkhead Box M1) • CDK1 (Cyclin-dependent kinase 1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
    |
    CCNE1 amplification • CCNE1 overexpression
    |
    gemcitabine • lunresertib (RP-6306)
    almost2years
    IGNITE: A phase II signal-seeking trial of adavosertib targeting recurrent high-grade, serous ovarian cancer with cyclin E1 overexpression with and without gene amplification. (ASCO 2022)
    The efficacy results in a biomarker-selected cohort of patients are promising with a higher response rate than reported in previous studies of adavosertib in unselected women with recurrent HGSC. Duration of response and progression free survival data will be presented as data matures.
    P2 data
    |
    CCNE1 (Cyclin E1) • MUC16 (Mucin 16, Cell Surface Associated)
    |
    CCNE1 amplification • CCNE1 overexpression • CCNE1 expression
    |
    adavosertib (AZD1775)
    almost2years
    KRAS wild-type pancreatic ductal adenocarcinoma: Molecular and therapeutic opportunities. (ASCO 2022)
    4 pts received FOLFIRINOX (FFX), 2 gemcitabine/nab-paclitaxel (GP) and tumor response were comparable to previously reported results. 1 received 1st-line pembrolizumab and remained on therapy at the time of analysis... The molecular profile of KRAS wt PDAC is highly heterogeneous and difficult to generalize. Novel approaches (e.g., basket trials) are needed to develop therapy for this rare PDAC subgroup.
    Tumor Mutational Burden • MSi-H Biomarker • PD(L)-1 Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MGMT (6-O-methylguanine-DNA methyltransferase) • CCNE1 (Cyclin E1) • KMT2D (Lysine Methyltransferase 2D) • RNF43 (Ring Finger Protein 43) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • MSH3 (MutS Homolog 3) • GNAS (GNAS Complex Locus) • RSPO3 (R-Spondin 3) • CA 19-9 (Cancer antigen 19-9)
    |
    TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • HER-2 overexpression • PTEN mutation • MET overexpression • KRAS wild-type • RAS wild-type • MET expression • CCNE1 overexpression • RNF43 mutation • MGMT underexpression • NTRK expression
    |
    Keytruda (pembrolizumab) • gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • leucovorin calcium