^
    11d
    Polyploid superficial uroepithelial bladder barrier cells express features of cellular senescence across the lifespan and are insensitive to senolytics. (PubMed, Aging Cell)
    These senescent UCs were not eliminated by the senolytic combination of Dasatinib and Quercetin...These findings illustrate the heterogeneity of cellular senescence in varied tissues, while also providing potential insights into the origin of urothelial cancer. We conclude that senescence of bladder uroepithelial cells plays a role in normal physiology, namely in their role as barrier cells, helping promote uroepithelial integrity and impermeability and maintaining the urine-blood barrier.
    Journal
    |
    CCND1 (Cyclin D1)
    |
    CCND1-H
    |
    dasatinib
    26d
    Clinical significance of Cyclin D1 by complete quantification detection in mantle cell lymphoma: positive indicator in prognosis. (PubMed, Diagn Pathol)
    Comprehensive Cyclin D1 quantification, especially above a threshold, significantly correlates with better overall survival in MCL. This highlights its prognostic importance in MCL management. Full quantification of CyclinD1 aids MCL prognosis, while QDB technology for biomarker quantification supports precise clinical prognostic stratification.
    Retrospective data • Journal
    |
    CCND1 (Cyclin D1)
    |
    CCND1 expression • CCND1-H
    2ms
    Functional variant rs9344 at 11q13.3 regulates CCND1 expression in multiple myeloma with t(11;14). (PubMed, Leukemia)
    Overexpression of PAX5 resulted in increased CCND1 expression. These results support the importance of rs9344 G enhancer in increasing CCND1 expression in MM.
    Journal
    |
    CCND1 (Cyclin D1) • PAX5 (Paired Box 5)
    |
    Chr t(11;14) • CCND1 overexpression • CCND1 expression • Chr t(11;14)(q13;q32) • PAX5 overexpression • CCND1-H
    3ms
    Clinicopathological characteristics and genetic features of young and senior Ewing sarcoma patients. (PubMed, Diagn Pathol)
    Clinicopathological characteristics and genetic features in young and senior EwS patients differed significantly. Targeting cell cycle dysregulation based on age subgroup may be a potential therapeutic strategy for Ewing sarcoma.
    Journal
    |
    CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • EWSR1 (EWS RNA Binding Protein 1) • STAG2 (Stromal Antigen 2) • ERG (ETS Transcription Factor ERG) • CHEK1 (Checkpoint kinase 1) • EPHA3 (EPH receptor A3) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor) • SLIT2 (Slit Guidance Ligand 2)
    |
    CCND1 amplification • CDK4 amplification • STAG2 mutation • CCND1 expression • EWSR1-FLI1 fusion • CCND1-H • EPHA3 mutation • CHEK1 expression
    7ms
    Mechanical shear flow regulates the malignancy of colorectal cancer cells. (PubMed, Kaohsiung J Med Sci)
    The results showed that lower shear flow increased mesenchymal characteristics and higher shear flow increased epithelial characteristics. Shear flow reduces the malignancy of CRC in their metastatic dispersal that opens up new ways to improve cancer therapies by applying a mechanical shear flow device.
    Journal
    |
    CCND1 (Cyclin D1) • CDH1 (Cadherin 1) • CASP9 (Caspase 9) • TWIST1 (Twist Family BHLH Transcription Factor 1) • TJP1 (Tight Junction Protein 1)
    |
    CCND1-H • CASP9 elevation
    8ms
    ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs. (PubMed, Cancer Res)
    Disruption of cyclin D1/CDK4 signaling led to loss of ASPS proliferative capacity, and combined inhibition of CDK4/6 and angiogenesis halted tumor growth in xenografts. These results define the ASPS oncogenic program, reveal mechanisms by which ASPSCR1::TFE3 controls tumor biology, and identify a strategy for therapeutically targeting tumor cell-intrinsic vulnerabilities.
    Journal
    |
    CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • TFE3 (Transcription Factor Binding To IGHM Enhancer 3) • ASPSCR1 (ASPSCR1 Tether For SLC2A4)
    |
    CCND1 expression • CCND1-H • TFE3 fusion
    12ms
    Cyclin D1 Based TPF Induction Chemotherapy for Oral Squamous Cell Carcinoma Patients at Clinical N2 Stage (clinicaltrials.gov)
    P2, N=48, Recruiting, Shanghai Jiao Tong University School of Medicine
    Trial completion date • Trial primary completion date
    |
    CCND1 (Cyclin D1)
    |
    CCND1 overexpression • CCND1 expression • CCND1-H
    |
    cisplatin • docetaxel • 5-fluorouracil
    1year
    Mutant N- and K-Ras Show Distinct Effects on Growth, Signaling and Drug Response in CRISPR-Cas Edited Alleles of a Myeloma Cell Line (ASH 2023)
    We are currently testing new pan-Ras inhibitors to determine if there are distinct responses between our N- and K-ras edited cells, and we are expanding testing to a wider panel of myeloma cell lines containing ras mutations in the context of other genetic abnormalities. Details of gene expression distinctions, pathways, and drug responses that distinguish mutNras and mutKras in myeloma will be presented.
    Preclinical
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CCND1 (Cyclin D1) • BCL2L1 (BCL2-like 1) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1)
    |
    KRAS mutation • NRAS mutation • RAS mutation • NRAS wild-type • CCND1 overexpression • CCND1 expression • CCND1-H • KRAS expression
    1year
    Phase Ib Clinical Study of Keynatinib (clinicaltrials.gov)
    P1, N=75, Recruiting, Medolution Ltd. | Trial completion date: Apr 2024 --> Apr 2028 | Trial primary completion date: Oct 2023 --> Oct 2027
    Trial completion date • Trial primary completion date
    |
    CCND1 (Cyclin D1)
    |
    CCND1 overexpression • CCND1 expression • CCND1-H
    |
    keynatinib (TL007)
    1year
    Mutant N- and K-Ras Show Distinct Effects on Growth, Signaling and Drug Response in CRISPR-Cas Edited Alleles of a Myeloma Cell Line (ASH 2023)
    We are currently testing new pan-Ras inhibitors to determine if there are distinct responses between our N- and K-ras edited cells, and we are expanding testing to a wider panel of myeloma cell lines containing ras mutations in the context of other genetic abnormalities. Details of gene expression distinctions, pathways, and drug responses that distinguish mutNras and mutKras in myeloma will be presented.
    Preclinical
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CCND1 (Cyclin D1) • BCL2L1 (BCL2-like 1) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1)
    |
    KRAS mutation • NRAS mutation • RAS mutation • NRAS wild-type • CCND1 overexpression • CCND1 expression • CCND1-H • KRAS expression
    over1year
    Quantification of cyclin D1 and D2 proteins in multiple myeloma identifies different expression patterns from those revealed by gene expression profiling. (PubMed, Haematologica)
    In conclusion, although one of the cyclins D is overexpressed at the mRNA level in almost all MM patients, in approximately half of the patients this does not translate into detectable protein. This suggests that cyclins D could not play an oncogenic role in a proportion of patients with MM.
    Journal
    |
    CCND1 (Cyclin D1) • CCND2 (Cyclin D2)
    |
    Chr t(11;14) • Chr t(4;14) • Chr t(14;16) • CCND1 expression • CCND1-H
    over1year
    Papillomatous breast lesions with atypical columnar cell features. (PubMed, J Clin Pathol)
    We present two papillomatous breast lesions with atypical CCL morphology and 16q loss, for which we propose the term papillary FEA.
    Journal
    |
    ER (Estrogen receptor) • PGR (Progesterone receptor) • CCND1 (Cyclin D1) • KRT5 (Keratin 5)
    |
    CCND1 expression • ER expression • PGR expression • CCND1-H
    2years
    Co-expressing genes with TACSTD2 and interacting microRNAs in patients with recurrent luminal breast cancers (EBCC 2022)
    TACSTD2 co-expressing AQP5 and LINC00052 and their interactions with STX4 and SRC could be interesting in further understanding Trop-2 positive luminal breast cancers in the relapsing state. Overexpression of miR-942 and depletion of miR-495 in recurrent tumors also require further experiments for validation.
    Clinical
    |
    CCND1 (Cyclin D1) • MIR495 (MicroRNA 495)
    |
    TROP2 expression • CCND1 expression • CCND1-H
    2years
    Clinical Genomic Analyses Demonstrate t(11; 14) Multiple Myeloma Retains B-Cell Biology and Distinct Mitochondrial Metabolism That Convey Increased Sensitivity to BCL-2 Inhibition By Venetoclax (ASH 2022)
    Using an integrated approach of transcriptomic and metabolomic profiling, t(11; 14) MM cells were confirmed to retain features of B-cell biology, including lower Mito metabolism that results in increased sensitivity to BCL-2 inhibition by Ven. Although these biological features are closely linked to t(11; 14), B-cell gene or Mito gene signatures did not serve as better biomarkers for predicting efficacy to Ven compared with t(11; 14) alone.
    Clinical • IO biomarker
    |
    CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • SDC1 (Syndecan 1)
    |
    BCL2 expression • CD20 expression • CCND1 expression • CCND1-H
    |
    Venclexta (venetoclax) • Vesanoid (tretinoin)
    2years
    Neratinib vs. Trastuzumab plus Ribociclib in ERBB2-positive breast cancer: Preclinical mechanistic efficacy study (SABCS 2022)
    Here, we evaluate the mechanistic efficacy and comparability of neratinib (N) (an irreversible pan-ERBB tyrosine kinase inhibitor) in combination with fulvestrant (F) against ribociclib (R) plus trastuzumab (T) in HER2-amplified breast cancer cells. Mechanistically, N+F was superior to T+R in terms of inhibition of HER2 and its downstream signaling in the HER2+/ER+ BC model. N+F induced significantly more apoptosis and inhibited cell proliferation compared to T+R. Additionally, N monotherapy was highly effective in HER2-amplified/ER-negative breast cancer cells with PIK3CA mutation.
    Preclinical • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BCL2 (B-cell CLL/lymphoma 2) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1)
    |
    HER-2 positive • HER-2 amplification • PIK3CA mutation • HER-2 expression • PIK3CA H1047R • ER negative • BCL2 expression • CCND1 expression • CCND1-H
    |
    Herceptin (trastuzumab) • Nerlynx (neratinib) • Kisqali (ribociclib) • fulvestrant
    over2years
    CCND1 Amplification Profiling Identifies a Subtype of Melanoma Associated With Poor Survival and an Immunosuppressive Tumor Microenvironment. (PubMed, Front Immunol)
    Melanoma with CCND1 amplification is an independent genomic subtype associated with a poor prognosis, an immunosuppressive TME, activated oxidative and lipid metabolism, and down-regulated angiogenesis. Therefore, avoiding ICIs and antiangiogenic agents, while employing CDK4/6 inhibitors alone or in combination with ICIs, and targeting oxidative and lipid metabolism pathways, may be effective therapeutic strategies for melanoma patients harboring CCND1 amplification.
    Journal • Tumor Mutational Burden • IO biomarker
    |
    BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • CD8 (cluster of differentiation 8) • CCND1 (Cyclin D1) • FGFR4 (Fibroblast growth factor receptor 4) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • B2M (Beta-2-microglobulin) • FLT1 (Fms-related tyrosine kinase 1) • CD4 (CD4 Molecule) • FGF2 (Fibroblast Growth Factor 2) • PDGFA (Platelet Derived Growth Factor Subunit A) • TAP1 (Transporter 1)
    |
    TMB-H • BRAF mutation • BRAF V600 • KIT mutation • NF1 mutation • CCND1 amplification • CD8 expression • BRAF amplification • CCND1-H
    over2years
    Rb tumor suppressor in small cell lung cancer: Combined genomic and immunohistochemical analysis with a description of a distinct Rb-proficient subset. (PubMed, Clin Cancer Res)
    This is the largest study to-date to concurrently analyze Rb by NGS and immunohistochemistry in SCLC, identifying a 6% rate of Rb proficiency. Pathologic-genomic data implicate NSCLC-related progenitors as a putative source of Rb-proficient SCLC. Consistent upstream Rb inactivation via CDKN2A/p16↓ and CCND1/cyclinD1↑ suggests potential utility of CDK4/6 inhibitors in this aggressive SCLC subset. The study also clarifies technical aspects of Rb status determination in clinical practice, highlighting the limitations of exon-only sequencing for RB1 interrogation.
    Journal
    |
    FGFR1 (Fibroblast growth factor receptor 1) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • CCND1 (Cyclin D1)
    |
    STK11 mutation • KEAP1 mutation • CDKN2A mutation • RB1 mutation • CCND1 amplification • CCND1 expression • CCND1-H • RB1 wild-type
    over2years
    Low expression of cytosolic NOTCH1 predicts poor prognosis of breast cancer patients. (PubMed, Am J Cancer Res)
    Expression of NOTCH1 mRNA was discordant with cell cycle-related genes. Regulation of NOTCH1 in breast cancer involves gene expression, protein localization and downstream signaling.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • NOTCH1 (Notch 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CDKN2C (Cyclin Dependent Kinase Inhibitor 2C) • CCNA1 (Cyclin A1)
    |
    ER positive • EGFR positive • CCND1 expression • NOTCH1 expression • CCND1-H
    over2years
    CCND1 Amplification in Breast Cancer -associations With Proliferation, Histopathological Grade, Molecular Subtype and Prognosis. (PubMed, J Mammary Gland Biol Neoplasia)
    Good correlation between CCND1 CNs in BCs and LNM was observed. Despite associations between high CCND1 CN and aggressive tumour characteristics, the prognostic impact of CCND1 CN remains unresolved.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • CCND1 (Cyclin D1)
    |
    CCND1 amplification • CCND1-H
    over2years
    The analysis of CCND1 amplification in Chinese patients with esophageal carcinoma. (ASCO 2022)
    The efficacy of ICIs in ESCA may be affected by multiple biomarkers, especially for TMB-H patients should be concerned about the higher frequency of CCND1 amplification, these patients may have a poorer benefit from immunotherapy.
    Clinical • Tumor Mutational Burden • IO biomarker
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FGF3 (Fibroblast growth factor 3) • FGF4 (Fibroblast growth factor 4)
    |
    TP53 mutation • TMB-H • CCND1 amplification • CCND1-H
    over2years
    Phase Ib Clinical Study of Keynatinib (clinicaltrials.gov)
    P1, N=75, Recruiting, Medolution Ltd. | Trial completion date: Apr 2023 --> Apr 2024 | Trial primary completion date: Oct 2022 --> Oct 2023
    Trial completion date • Trial primary completion date
    |
    CCND1 (Cyclin D1)
    |
    CCND1 overexpression • CCND1 expression • CCND1-H
    |
    keynatinib (TL007)
    over2years
    Cyclin D1 mediated by the nuclear translocation of nuclear factor kappa B exerts an oncogenic role in lung cancer. (PubMed, Bioengineered)
    Inhibition of PI3K/AKT pathway activity or suppression of NF-κB translocation in cells with high CCND1 expression was found to significantly reduce the activity of lung cancer cells in vitro and in vivo. Our data revealed that NF-κB/CCND1/PI3K/AKT axis could act as a prospective diagnostic biomarker and a therapeutic option for lung cancer.
    Journal
    |
    CCND1 (Cyclin D1) • RELA (RELA Proto-Oncogene)
    |
    CCND1 overexpression • CCND1 expression • CCND1-H
    almost3years
    Expression of Cyclin D1 gene in ovarian cancer and effect of silencing its expression on ovarian cancer cells based on the Oncomine database. (PubMed, Bioengineered)
    CCND1 gene is highly expressed in ovarian cancer tissue and related to prognosis. Preoperative evaluation of CCND1 gene expression in ovarian cancer patients may benefit the assessment of risk and prognosis.
    Journal
    |
    CCND1 (Cyclin D1)
    |
    CCND1 expression • CCND1 underexpression • CCND1-H
    almost3years
    Uveal Melanoma and Paraneoplastic Perivascular Dermal Melanocytic Proliferation in the Setting of Bilateral Diffuse Uveal Melanocytic Proliferation: The Potential Role of the Hepatocyte Growth Factor/c-Met Axis in Their Pathogenesis. (PubMed, Ocul Oncol Pathol)
    Two patients, with non-small cell lung carcinoma treated with pembrolizumab, developed bilateral diffuse uveal melanocytic proliferation (BDUMP) with interesting histopathological features...These cells also expressed c-Met protein. These observations implicate the HGF/c-Met axis in the pathogenesis of BDUMP, the uveal melanomas in the ciliary body and choroid in the first patient and the paraneoplastic dermal melanocytic proliferation in the second patient.
    Journal • PD(L)-1 Biomarker
    |
    MET (MET proto-oncogene, receptor tyrosine kinase) • CCND1 (Cyclin D1) • HGF (Hepatocyte growth factor) • PRAME (Preferentially Expressed Antigen In Melanoma)
    |
    MET expression • CCND1 expression • CCND1-H
    |
    Keytruda (pembrolizumab)
    3years
    Detection of CCND1 Overexpression By RNA-Seq from Tna Samples As a Surrogate for t(11:14) Translocation Traditionally Measured By FISH in Multiple Myeloma Patients for Improved Patient Care (ASH 2021)
    In this study we evaluated our existing NGS assay for CCND1 overexpression using TNA as a surrogate for traditional FISH, while demonstrating the accuracy of the RNA quantitation by NGS using qRT-PCR. We developed an RNA-seq based CCND1 expression assay that could be used to complement traditional FISH testing especially if there is limited specimen. The confirmation of overexpression in FISH negative samples may suggest new ways to improve MM patients risk stratification and treatment.
    Clinical
    |
    CCND1 (Cyclin D1) • IGH (Immunoglobulin Heavy Locus) • SDC1 (Syndecan 1) • RPL5 (Ribosomal Protein L5)
    |
    Chr t(11;14) • CCND1 overexpression • CCND1 expression • Chr t(11;14)(q13;q32) • CCND1-H
    3years
    Comprehensive Analysis of the Tumoral and Microenvironmental Transcriptome of Lymph Nodes and Bone Marrow in Mantle Cell Lymphoma (ASH 2021)
    Besides being a useful tool at diagnosis, RT-MLPA successfully allowed for a concomitant approach of a large number of transcripts and thus a precise evaluation of intrinsic prognostic and extrinsic features of MCL. Important, yet seldom described, modulations of T-cells, NK cells, macrophages and cytokines were observed, with different profiles segregating MCL with aggressive morphology and those with resistance to treatment.
    PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • PD-L2 (Programmed Cell Death 1 Ligand 2) • CD163 (CD163 Molecule) • CSF1 (Colony stimulating factor 1) • IL10 (Interleukin 10) • CD14 (CD14 Molecule) • TGFB1 (Transforming Growth Factor Beta 1) • CD40LG (CD40 ligand) • SOX11 (SRY-Box Transcription Factor 11)
    |
    PD-L1 expression • PD-L1 overexpression • CCND1 expression • CCND1-H • SOX11 expression
    3years
    Utilising artificial intelligence (AI) for analysing multiplex genomic and magnetic resonance imaging (MRI) data to develop multimodality predictive system for personalised neoadjuvant treatment of breast cancer (BC) (SABCS 2021)
    Our predictive models were trained in a local cohort of 400 BC (300 HER2 negative (HER2-) received 8 cycles of anthracycline & Taxane & 100 HER2 positive (HER2+) received Trastuzumab, anthracycline &Taxane) & was validated in 150 patients from local clinical trial patients... A predictive model was developed for HER2+ and another for HER2- BC with >= 80% accuracy prediction of pCR. AI & multiplex technology could enable robust biomarker discovery.
    Clinical
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • CCND1 (Cyclin D1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • RAD51 (RAD51 Homolog A) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • CDK6 (Cyclin-dependent kinase 6) • AGR2 (Anterior gradient 2) • GRB7 (Growth Factor Receptor Bound Protein 7) • CXXC5 (CXXC Finger Protein 5) • FOXM1 (Forkhead Box M1) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1) • BAG1 (BAG Cochaperone 1) • FOXC1 (Forkhead Box C1) • SFRP1 (Secreted frizzled related protein 1) • TP73 (Tumor Protein P73) • MCM3 (Minichromosome maintenance complex component 3)
    |
    HER-2 positive • HER-2 overexpression • HER-2 negative • HER-2 expression • CCND1-H
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay • MammaPrint • Oncotype DX Breast Recurrence Score®Test
    |
    Herceptin (trastuzumab)
    3years
    Whole genome sequencing-based circulating tumor DNA profiling of metastatic breast cancer patients for molecular characterization and therapy response prediction (SABCS 2021)
    The ctDNA shallowHRD score was highest in TNBC patients among subtypes, and TNBC patients with high shallowHRD score (≥10) showed high response rate on (58.3% versus 28.6%) on platinum-based chemotherapy. Conclusion LP WGS-based ctDNA analysis provides a robust tool for non-invasive genomic clustering, therapy response prediction, and HRD estimation in metastatic breast cancer patients.
    Clinical • Circulating tumor DNA
    |
    EGFR (Epidermal growth factor receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • FGFR1 (Fibroblast growth factor receptor 1) • HRD (Homologous Recombination Deficiency) • CCND1 (Cyclin D1) • BCL6 (B-cell CLL/lymphoma 6)
    |
    HRD • FGFR1 amplification • MYC amplification • PIK3CA amplification • CCND1-H
    3years
    CircRNA Circ-CCND1 Aggravates Hepatocellular Carcinoma Tumorigenesis by Regulating the miR-497-5p/HMGA2 Axis. (PubMed, Mol Biotechnol)
    Circ-CCND1 plays a cancer-promoting role in HCC by modulating the miR-497-5p/HMGA2 axis. Therefore, targeting circ-CCND1 is likely to be a promising therapeutic strategy for HCC.
    Journal
    |
    CCND1 (Cyclin D1) • HMGA1 (High Mobility Group AT-Hook 1) • HMGA2 (High mobility group AT-hook 2) • MIR497 (MicroRNA 497)
    |
    CCND1 expression • CCND1-H
    over3years
    Epithelial-mesenchymal transition (EMT) in vulvar cancer with and without inguinal lymph node involvement. (PubMed, J Cancer Res Clin Oncol)
    The present study shows no differences in the expression of EMT markers between node positive and node negative vulvar cancers. The evaluation of immunostaining within the micro-anatomical context indicates that an EMT-phenotype is restricted to the tumor cells at the front of invasion. Paired analyses of vulvar carcinomas and their lymph node deposits suggest mesenchymal-epithelial transition (MET) in the metastatic deposits. Immunohistochemical staining results may suggest that EMT is more prevalent in vulvar cancer with aberrant p53 staining.
    Journal
    |
    TP53 (Tumor protein P53) • CCND1 (Cyclin D1) • CDH1 (Cadherin 1) • VIM (Vimentin)
    |
    CCND1 expression • TP53 expression • CDH1 expression • VIM expression • CCND1-H
    over3years
    [VIRTUAL] Precision medicine development and validation of a multi-fluorescent automated assay to quantify BCL2 and CCND1 expression in CD138 positive bone marrow multiple myeloma (MM) cells (ECP 2021)
    We identified MM patients with CD138+ cells expressing high CCND1 and/or high BCL2 expression utilising automated triple immunofluorescent staining of bone marrow trephines. CCND1 and BCL2 expressions, in accordance with the literature, surpasses the t(11;14) subgroups defined traditionally by FISH, identifying a larger cohort of patients that could potentially benefit from the addition of venetoclax in their therapeutic algorithm.
    IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • CCND1 (Cyclin D1) • SDC1 (Syndecan 1)
    |
    Chr t(11;14) • Chr t(4;14) • BCL2 expression • CCND1 overexpression • CCND1 expression • SDC1 positive • CCND1-H
    |
    Venclexta (venetoclax)
    over3years
    CCND1 copy number increase and cyclin D1 expression in acral melanoma: a comparative study of fluorescence in situ hybridization and immunohistochemistry in a Chinese cohort. (PubMed, Diagn Pathol)
    High-level increase in the CCND1 copy number can induce high cyclin D1 protein expression in acral melanomas. However low-level increase and normal CCND1 copy number have no obvious correlation with protein expression. Cyclin D1 IHC cannot serve as a surrogate for CCND1 FISH in acral melanomas.
    Journal
    |
    CCND1 (Cyclin D1)
    |
    CCND1 overexpression • CCND1 expression • CCND1-H
    over3years
    Decreased ERβ expression and high cyclin D1 expression may predict early CRC recurrence in high-risk Duke's B and Duke's C stage. (PubMed, J BUON)
    Early recurrence of CRC in high-risk Duke's B and Duke's C stage relates with reduced ERβ expression and the high cyclin D1 expression, so they could be considered independent prognostic factors, especially in patients in advanced T stage.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • CCND1 (Cyclin D1)
    |
    BCL2 expression • CCND1 expression • CCND1-H
    over3years
    [VIRTUAL] CCND1 amplification profiling identifies a subtype of melanoma associated with poor survival and an immunosuppressive tumor microenvironment. (ASCO 2021)
    Melanoma with CCND1 amplificationis an independent genomic subtype associated with a poor prognosis, an immunosuppressive TME, activated oxidative and lipid metabolism, and down-regulated angiogenesis . Taken together, avoiding ICIs and antiangiogenic agents, while employing CDK4/6 inhibitors alone or in combination with ICIs, targeting oxidative and lipid metabolism pathway may be effective and promising therapeutic strategies for melanoma patients harboring CCND1 amplification.
    Tumor Mutational Burden • IO biomarker
    |
    BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • CD8 (cluster of differentiation 8) • CCND1 (Cyclin D1) • FGFR4 (Fibroblast growth factor receptor 4) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • FLT1 (Fms-related tyrosine kinase 1) • FGF2 (Fibroblast Growth Factor 2) • PDGFA (Platelet Derived Growth Factor Subunit A)
    |
    TMB-H • BRAF mutation • BRAF V600 • KIT mutation • NF1 mutation • CCND1 amplification • BRAF amplification • CCND1-H
    over3years
    Dual blockade of EGFR and CDK4/6 delays head and neck squamous cell carcinoma progression by inducing metabolic rewiring. (PubMed, Cancer Lett)
    Here, we aimed to determine the combined effect of palbociclib (CDK4/6) and afatinib (panEGFR) inhibitors as an effective strategy to target HNSCC. Additionally sub-cutaneous and genetically engineered mouse model (K14-CreER;LSL-Kras;Trp53) studies indicated reduction in the tumor growth and delayed tumor progression, respectively. This study collectively demonstrates that dual targeting may be a critical therapeutic strategy in blocking tumor progression via inducing metabolic alteration and warrants clinical evaluation.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4)
    |
    CCND1 expression • CCND1-H
    |
    Gilotrif (afatinib) • Ibrance (palbociclib)
    almost4years
    Phase Ib Clinical Study of Keynatinib (clinicaltrials.gov)
    P1, N=75, Recruiting, Medolution Ltd.
    Clinical • New P1 trial
    |
    CCND1 (Cyclin D1)
    |
    CCND1 overexpression • CCND1 expression • CCND1-H
    |
    keynatinib (TL007)
    almost4years
    Berberine Inhibits Telomerase Activity and Induces Cell Cycle Arrest and Telomere Erosion in Colorectal Cancer Cell Line, HCT 116. (PubMed, Molecules)
    Telomerase activity and level was significantly decreased, and telomere erosion followed suit. In summary, our findings suggested that berberine could decrease telomerase activity and level of HCT 116, which in turn inhibits the proliferative ability of the cells.
    Preclinical • Journal
    |
    TERT (Telomerase Reverse Transcriptase) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4)
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    CCND1-H
    almost4years
    AURKB promotes gastric cancer progression via activation of CCND1 expression. (PubMed, Aging (Albany NY))
    Furthermore, we show that AZD1152, a specific inhibitor of AURKB, can suppress the expression of CCND1 in the gastric cancer cells and inhibit cell proliferation in vitro and in vivo. Importantly, we found that high AURKB and CCND1 expression levels are correlated with shorter overall survival of gastric cancer patients. This study demonstrates that AURKB promotes gastric tumorigenesis potentially through epigenetically activating CCND1 expression, suggesting AURKB as a promising therapeutic target in gastric cancer.
    Journal
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    CCND1 (Cyclin D1) • AURKB (Aurora Kinase B)
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    CCND1 expression • CCND1-H
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    barasertib-HQPA (AZD2811) • barasertib (AZD1152)