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CCND1 (G1/S-specific cyclin-D1) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker, a fusion partner and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Breast cancer, Skin cancer, Multiple myeloma and 5 more.
Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase.
CIViC holds 23 clinical evidence items and 0 assertions across 5 variants, naming Palbociclib, Tamoxifen, Ribociclib and Sorafenib and others. Open Targets scores its association with cancer at 0.86 (direct and indirect evidence; datatypes clinical 0.97, genetic literature 0.61, affected pathway 0.80, literature 1.00, genetic association 0.70, somatic mutation 0.93, animal model 0.56). IntOGen calls it a driver in 4 cohorts (2 activating, 2 loss-of-function), covering Head and Neck Squamous Cell Carcinoma, Plasma Cell Myeloma, Endometrial Carcinoma.
In plain words · CCND1 (G1/S-specific cyclin-D1) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker, a fusion partner and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Breast cancer, Skin cancer, Multiple myeloma and 5 more.
CCND1 (G1/S-specific cyclin-D1) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker, a fusion partner and a DNA repair gene, and an approved or late-stage drug is recorded against it. Tied to Breast cancer, Skin cancer, Multiple myeloma and 5 more.
Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition.
No product in this corpus aims at CCND1 yet. Transcription factors have no pocket to plug, so drugs either degrade them or block the partner protein they need to dock on DNA.
Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance) and a fusion partner (UniProt records a translocation), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA CCND1: RNA low tissue specificity; high antibody staining in 15 normal tissues; highest cancer staining renal cancer (11 of 12 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Breast cancer (all types), Skin cancer (all types), Multiple myeloma, Ovarian cancer, Head and neck squamous cell carcinoma, Renal cell carcinoma, Colorectal cancer and more); Open Targets associates it with 4 specific cancer types at or above 0.5 (breast cancer, breast carcinoma, prostate carcinoma, plasma cell myeloma). (Rule 6 of scripts/fetch-target-specificity.ts.)
Sources: UniProt P24385; CIViC gene CCND1; IntOGen CCND1; Human Protein Atlas CCND1 tissue; Open Targets ENSG00000110092 associations
First described 1991. Earliest sequence paper UniProt cites for the protein: Motokura et al, Nature, 1991, "A novel cyclin encoded by a bcl1-linked candidate oncogene". Source.
Sources: HGNC HGNC:1582 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P24385 (protein name, function text, keywords and locations (REST API)); CIViC gene CCND1 (23 evidence items, 0 assertions, 5 variants; diseases: Breast Cancer, Lung Non-small Cell Carcinoma, Mantle Cell Lymphoma, Cancer, Ovarian Cancer and 8 more (GraphQL API, CC0)); Open Targets ENSG00000110092 (association with cancer (MONDO_0004992) 0.86; per-cancer scores at or above 0.5: colorectal cancer 0.58, prostate cancer 0.54, endometrial cancer 0.51, melanoma 0.63, plasma cell myeloma 0.53, non-Hodgkin lymphoma 0.57 (GraphQL API, CC0)); IntOGen CCND1 (driver in 4 cohorts (Act 2, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also a substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Location: Nucleus; Cytoplasm; Nucleus membrane (UniProt). Locus 11q13.3 (HGNC).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Bronchus, Cervix, Colon, Duodenum, Endometrium, Esophagus, Fallopian tube, Hippocampus.
HPA CCND1 tissue · HPA CCND1 pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
A second randomised confirmation that adding a Bruton tyrosine kinase inhibitor to first-line bendamustine-rituximab delays progression in older patients with mantle cell lymphoma, with a toxicity profile that did not improve as much as the drug's selectivity promised.
The authors' conclusion is that ibrutinib-rituximab should be considered a new standard-of-care option for first-line treatment of older patients with mantle-cell lymphoma. The subgroup split means it is clearly better than R-CHOP and roughly equivalent to bendamustine-rituximab.
Twenty-eight extra months of progression-free survival, with no survival gain and a high rate of severe adverse events in both arms. It set up the two trials that followed: ECHO, which substituted a more selective inhibitor, and ENRICH, which removed the chemotherapy.
One of the few maintenance strategies in lymphoma that improved overall survival rather than only progression-free survival, and the reason three years of rituximab became standard after autologous transplantation in mantle cell lymphoma.
Query for this target: (TITLE:"CCND1" OR ABSTRACT:"CCND1" OR TITLE:"cyclin D1" OR ABSTRACT:"cyclin D1" OR TITLE:"G1/S-specific cyclin-D1" OR ABSTRACT:"G1/S-specific cyclin-D1" OR TITLE:"U21B31" OR ABSTRACT:"U21B31" OR TITLE:"BCL1" OR ABSTRACT:"BCL1" OR TITLE:"D11S287E" OR ABSTRACT:"D11S287E") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CCND1, not a curated reading list.
Shares t(11;14), cyclin D1 and SOX11, Mantle cell lymphoma, Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting, Skin cancer (all types).
Shares LyMa, Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma, SHINE, ENRICH.
Shares Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma, Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma, SHINE, Mantle cell lymphoma.
Shares LyMa, Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma, Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma, SHINE.
Shares Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma, Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma, SHINE, Mantle cell lymphoma.
Shares Checkpoint (two meanings), Skin cancer (all types), CIViC, IntOGen.
Shares Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma, Ibrutinib and rituximab versus immunochemotherapy in patients with previously untreated mantle cell lymphoma (ENRICH): a randomised, open-label, phase 2/3 superiority trial, Mantle cell lymphoma, Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting.
Shares A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL, Acalabrutinib plus bendamustine-rituximab in untreated mantle cell lymphoma, Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma, SHINE.