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    GENE:

    FOXC1 (Forkhead Box C1)

    i
    Other names: FOXC1, Forkhead Box C1, FREAC3, Forkhead-Related Transcription Factor 3, Forkhead-Related Protein FKHL7, Forkhead Box Protein C1, FREAC-3, FKHL7, IGDA, IHG1, ARA, Forkhead/Winged Helix-Like Transcription Factor, Forkhead, Drosophila, Homolog-Like, Forkhead-Related Activator 3, Forkhead Box C1 Protein, Myeloid Factor-Delta, ASGD3, IRID1, RIEG3
    20d
    Metronomic capecitabine as extended adjuvant chemotherapy for early triple-negative breast cancer (SYSUCC-001): updated 10-year outcomes and post-hoc exploratory biomarker analysis from a randomised, phase 3 trial. (PubMed, Lancet Oncol)
    In this exploratory, long-term analysis, extended adjuvant metronomic capecitabine provided durable disease-free survival benefit in early triple-negative breast cancer, although the findings should be interpreted with caution given the post-hoc nature of the analysis. Patients with FOXC1-high tumours showed a survival advantage with capecitabine versus observation; if this finding is validated, FOXC1-driven patient selection might be useful to optimise therapeutic responses.
    Clinical • P3 data • Retrospective data • Journal
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    FOXC1 (Forkhead Box C1)
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    capecitabine
    2ms
    In-Silico discovery of Pediatric Acute-Myeloid-Leukemia (pAML) causing druggable molecular signatures highlighting their pathogenetic processes and therapeutic agents through single-cell RNA-Seq profile analysis. (PubMed, PLoS One)
    Subsequently, three potential therapeutic candidates (IRINOTECAN HYDROCHLORIDE, IMATINIB and IBRUTINIB) were disclosed through an integrative strategy combining molecular docking, drug-likeness, ADME/T, and DFT analyses. Molecular dynamics (MD) simulation studies for the top three drug-target complexes indicated the stability of complexes. Thus, the findings potentially offer valuable insights for pAML pathogenesis and effective therapeutic candidates for pAML patients.
    Journal
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    TP53 (Tumor protein P53) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • MCL1 (Myeloid cell leukemia 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CD4 (CD4 Molecule) • GATA2 (GATA Binding Protein 2) • FOXC1 (Forkhead Box C1) • MIR15A (MicroRNA 15a) • MIRLET7E (MicroRNA Let-7e) • RELA (RELA Proto-Oncogene) • SOD2 (Superoxide Dismutase 2)
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    Imbruvica (ibrutinib) • imatinib • irinotecan
    2ms
    Machine learning and WGCNA reveal the PVT1/miR-143-3p/CDK1 ceRNA axis as a key regulator in NSCLC. (PubMed, Biochem Biophys Rep)
    We also identified the PVT1/miR-143-3p/CDK1 axis and its associated transcription factors (FOXC1, YY1, and GATA2) as a potential regulatory network for additional investigations. These findings increase the understanding of NSCLC molecular processes and provide a foundation for developing targeted therapies and diagnostic tools.
    Journal
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    TOP2A (DNA topoisomerase 2-alpha) • AURKA (Aurora kinase A) • GATA2 (GATA Binding Protein 2) • CDK1 (Cyclin-dependent kinase 1) • FOXC1 (Forkhead Box C1) • MIR143 (MicroRNA 143) • PVT1 (Pvt1 Oncogene) • BUB1B (BUB1 Mitotic Checkpoint Serine/Threonine Kinase B) • YY1 (YY1 Transcription Factor)
    2ms
    Prognostic Interplay of Caveolin1 and FOXC1 in Early Nonmetastatic Triple Negative Breast Cancer Undergoing Neoadjuvant Chemotherapy. (PubMed, Appl Immunohistochem Mol Morphol)
    Both CAV1 and FOXC1 may serve as adverse prognostic indicators in TNBC. Their overexpression suggests a potential lack of benefit from NAC, indicating that targeted therapies against these markers might be more effective.
    Journal
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    CAV1 (Caveolin 1) • FOXC1 (Forkhead Box C1)
    3ms
    FOXC1 expression profile in invasive breast carcinomas and its relationship with prognostic parameters. (PubMed, Pol J Pathol)
    On the other hand, FOXC1 was significantly associated with high proliferation index, high-grade tumour, and prognostic stage. These findings sug-gest that high FOXC1 expression may indicate aggressive behaviour and may be a predictive marker for poor prognosis.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • FOXC1 (Forkhead Box C1)
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    HER-2 expression
    3ms
    m6A-modified circCD2AP suppressed ferroptosis in bladder cancer by upregulating FOXC1 to promote PARK7 transcriptional activity. (PubMed, Chin Med J (Engl))
    METTL3-mediated m6A modification drives circCD2AP overexpression, which is subsequently exported to the cytoplasm with enhanced efficiency mediated by YTHDC1. Cytoplasmic circCD2AP stabilizes FOXC1 mRNA, enabling FOXC1-dependent transcriptional activation of PARK7. This axis suppresses ferroptosis and promotes BCa progression, revealing a novel therapeutic target.
    Journal
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    FOXC1 (Forkhead Box C1) • YTHDC1 (YTH Domain Containing 1) • IGF2BP3 (Insulin Like Growth Factor 2 MRNA Binding Protein 3) • METTL3 (Methyltransferase Like 3)
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    erastin
    3ms
    The Emerging Landscape of LINC01123 in Cancer: Roles, Mechanisms, and Clinical Significance. (PubMed, Curr Drug Targets)
    LINC01123 has potential as a novel prognostic biomarker and therapeutic target for cancer. Further research is needed to elucidate its mechanisms and clinical applications fully.
    Journal
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • FOXC1 (Forkhead Box C1) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)
    3ms
    RNF180 suppressed aggressiveness by degrading NOTCH1, TRIM24 and FOXC1, and chemoresistance by degrading ACC1 and ACLY in colorectal cancer. (PubMed, Int Immunopharmacol)
    RNF180-correlated genes were involved in neuroactive ligand-receptor interaction, glycosaminoglycan binding, ECM structural constituents and organization, receptor ligand activity, cell adhesion, mRNA splicing and so forth in CRC. The expression of RNF180 may be used as a biomarker for the diagnosis, as a prognostic indicator, and as a gene therapy target of CRC.
    Journal
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    NOTCH1 (Notch 1) • FOXC1 (Forkhead Box C1) • TRIM24 (Tripartite Motif Containing 24) • ACACA (Acetyl-CoA Carboxylase Alpha) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
    4ms
    FASCINATE-N: Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy (clinicaltrials.gov)
    P2, N=716, Recruiting, Fudan University | Trial completion date: Sep 2025 --> Sep 2028 | Trial primary completion date: Dec 2024 --> Dec 2026
    Trial completion date • Trial primary completion date
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    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • CD8 (cluster of differentiation 8) • FOXC1 (Forkhead Box C1)
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    Herceptin (trastuzumab) • carboplatin • Focus V (anlotinib) • Perjeta (pertuzumab) • AiRuiKa (camrelizumab) • AiTan (rivoceranib) • Irene (pyrotinib) • albumin-bound paclitaxel • cyclophosphamide • letrozole • epirubicin • trastuzumab rezetecan (SHR-A1811) • AiRuiYi (fluzoparib) • Andewei (benmelstobart) • AiRuiKang (dalpiciclib) • goserelin acetate • famitinib (SHR 1020) • Yidafan (ivonescimab) • AiRuiLi (adebrelimab) • SHR-4602 • TQB2102 • TQB2868 • anbenitamab repodatecan (JSKN003) • tizetatug rezetecan (SHR-A1921)
    5ms
    Biomarker discovery for early breast cancer diagnosis using machine learning on transcriptomic data for biosensor development. (PubMed, Comput Biol Med)
    The influence of MLA on F1 Macro and Accuracy was not statistically significant. Altogether, the genetic biomarkers identified in this study hold potential for use in biosensors aimed at breast cancer diagnosis and treatment.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • FOXA1 (Forkhead Box A1) • FOXC1 (Forkhead Box C1) • MFSD2A (MFSD2 Lysolipid Transporter A) • MLPH (Melanophilin) • SFRP1 (Secreted frizzled related protein 1) • CACNA1H (Calcium Voltage-Gated Channel Subunit Alpha1 H)
    5ms
    From heterogeneity to hope: emerging markers in triple-negative breast cancer research. (PubMed, Med Oncol)
    Summary This systematic analysis of the literature indicates that IDO1, DCLK1, and FOXC1 are promising molecular markers for prognosis, risk stratification of recurrence, individualized treatment strategies, and identification of new therapeutic targets in TNBC. However, further research, including standardized evaluation methods, larger cohort studies, and additional clinical trials, is essential for their successful clinical implementation.
    Review • Journal • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • IDO1 (Indoleamine 2,3-dioxygenase 1) • FOXC1 (Forkhead Box C1)
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    HER-2 expression
    6ms
    FOXC1 expression predicts capecitabine efficacy in triple-negative breast cancer patients from the GEICAM_CIBOMA trial. (PubMed, Clin Cancer Res)
    This ambispective GEICAM_CIBOMA translational analysis validated FOXC1-based basal-like/non-basal subtyping as a pragmatic alternative to PAM50 subtyping and independently predicted the benefit of adding capecitabine to standard (neo)adjuvant chemotherapy in TNBC.
    Journal
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    FOXC1 (Forkhead Box C1)
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    Prosigna™ Breast Cancer Prognostic Gene Signature Assay
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    capecitabine