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BIOMARKER:

CDK4 amplification

i
Other names: CDK4, PSK-J3, Cyclin-dependent kinase 4
Entrez ID:
Related biomarkers:
2d
Ribociclib (LEE011) in Preoperative Glioma and Meningioma Patients (clinicaltrials.gov)
P1, N=48, Active, not recruiting, Nader Sanai | Trial completion date: Jan 2024 --> Jan 2025
Trial completion date
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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CDKN2A deletion • CCND1 amplification • CDK4 amplification
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Kisqali (ribociclib)
2d
LY3214996 Plus Abemaciclib in Recurrent Glioblastoma Patients (clinicaltrials.gov)
P1, N=50, Recruiting, Nader Sanai | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Dec 2023 --> Dec 2024
Trial completion date • Trial primary completion date • Combination therapy
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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CDK4 amplification
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Verzenio (abemaciclib) • temuterkib (LY3214996)
8d
Bone metastasis in non-small-cell lung cancer: genomic characterization and exploration of potential targets. (PubMed, Ther Adv Med Oncol)
Compared to the primary tumors of NSCLC, the genome of BMs showed an increased proportion of amplification and a decreased proportion of gene substitution/indel. Furthermore, the CDK4 amplification ratio seemed to be elevated in NSCLC patients with BM which may be associated with poor OS and RFS.
Journal
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CDK4 (Cyclin-dependent kinase 4)
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CDK4 amplification
22d
Myxoid pleomorphic liposarcoma. (PubMed, Histol Histopathol)
The aim of this review article is to provide a comprehensive summary of previously documented case reports and studies related to MPLs. By shedding light on the intricate details of MPLs, researchers and clinicians can gain valuable insights that may pave the way for improvements in diagnosis, treatment, and patient outcomes in the future.
Review • Journal
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MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • EWSR1 (EWS RNA Binding Protein 1) • FUS (FUS RNA Binding Protein) • DDIT3 (DNA-damage-inducible transcript 3)
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CDK4 amplification
1m
Adult epithelioid glioblastoma exhibits an extremely poor prognosis and high frequency of SWI/SNF complex mutation: Insights from a retrospective study. (PubMed, Int J Cancer)
Adult eGBM carried a dismal prognosis compared to GBM with IDH and H3 wild-type (typical GBM) (OS: 13.89 vs 24.30 months; P = .003) and even typical GBM without MGMT promoter methylation (OS: 13.89 vs 22.08 months; P = .036). Based on these findings, it can be concluded that adult eGBM harbors a high frequency of the 7+/10- signature and alterations in the MAPK pathway, SWI/SNF complex and cyclin-related genes and portends an extremely poor prognosis.
Retrospective data • Journal
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BRAF (B-raf proto-oncogene) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ARID1B (AT-Rich Interaction Domain 1B)
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BRAF V600E • BRAF V600 • CDKN2A deletion • MGMT promoter methylation • CDK4 amplification • TERT mutation • ARID1B mutation • TERT promoter mutation • BRAF amplification
1m
CDK4/MDM2 Amplification Is a Rare Targetable Genomic Event in TP53/RB1-Wildtype Uterine Leiomyosarcoma (USCAP 2024)
Overall, in our uLMS analysis, CDK4 and/or MDM2 amplification was identified in a small subset (2%) of uLMS, the majority of which are TP53/RB1-wildtype. This may suggest that CDK4/MDM2 amplification can be an alternative tumorigenic mechanism in this distinct class of uLMS, which may have therapeutic clinical implications, including possible use of specific cyclin-dependent kinase inhibitors.
Tumor mutational burden
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • MDM2 amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification • RB1 wild-type • CDK4 mutation
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FoundationOne® Heme CDx
1m
CDK4/MDM2 Amplification Is a Rare Targetable Genomic Event in TP53/RB1-Wildtype Uterine Leiomyosarcoma (USCAP 2024)
Overall, in our uLMS analysis, CDK4 and/or MDM2 amplification was identified in a small subset (2%) of uLMS, the majority of which are TP53/RB1-wildtype. This may suggest that CDK4/MDM2 amplification can be an alternative tumorigenic mechanism in this distinct class of uLMS, which may have therapeutic clinical implications, including possible use of specific cyclin-dependent kinase inhibitors.
Tumor mutational burden
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • MDM2 amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification • RB1 wild-type • CDK4 mutation
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FoundationOne® Heme CDx
1m
Trial primary completion date
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CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6)
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CCND1 amplification • CDK4 amplification • CCND1 mutation
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OncoPanel™ Assay
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Verzenio (abemaciclib)
2ms
Soft Tissue Sarcomas with Chromosomal Alterations in the 12q13-15 Region: Differential Diagnosis and Therapeutic Implications. (PubMed, Cancers (Basel))
This suggests the potential use of MDM2 or CDK4 inhibitors in neoplasms where alterations in these genes do not aid the pathological diagnosis but may help identify potential therapeutic targets. In this review, we delve into the diagnosis and therapeutic implications of tumors with genetic alterations involving the chromosomal region 12q13-15, mainly MDM2, CDK4, and GLI1.
Review • Journal
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MDM2 (E3 ubiquitin protein ligase) • GLI1 (GLI Family Zinc Finger 1) • STAT6 (Signal transducer and activator of transcription 6) • DDIT3 (DNA-damage-inducible transcript 3)
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CDK4 amplification • MDM2 amplification + CDK4 amplification
2ms
Clinicopathological and Molecular Characteristics of IDH-Wildtype Glioblastoma with FGFR3::TACC3 Fusion. (PubMed, Biomedicines)
Our observations suggest that F3T3-positive GBM is a distinct molecular subgroup of the IDH-wildtype GBM. Both clinicians and pathologists should consider this rare entity in the differential diagnosis of diffuse astrocytic glioma to make an accurate diagnosis and to ensure appropriate therapeutic management.
Journal
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EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TERT (Telomerase Reverse Transcriptase) • TACC3 (Transforming acidic coiled-coil containing protein 3) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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TP53 mutation • EGFR mutation • EGFR amplification • PTEN mutation • MDM2 amplification • CDKN2A deletion • CDKN2A mutation • CDK4 amplification • FGFR3 fusion • TERT mutation • IDH wild-type • TERT promoter mutation • CDK4 mutation
2ms
Trial initiation date • Combination therapy • Surgery
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MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
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CDK4 amplification
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Verzenio (abemaciclib)
3ms
Small-molecule inhibition of kinesin KIF18A reveals a mitotic vulnerability enriched in chromosomally unstable cancers. (PubMed, Nat Cancer)
In mice, inhibition of KIF18A leads to robust anti-cancer effects with tumor regression observed in human HGSOC and TNBC models at well-tolerated doses. Collectively, our results provide a rational therapeutic strategy for selective targeting of CIN cancers via KIF18A inhibition.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • CCNE1 (Cyclin E1) • CDK6 (Cyclin-dependent kinase 6) • KIF18A (Kinesin Family Member 18A)
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TP53 mutation • CCNE1 amplification • CDK4 amplification
3ms
Rare myxoid pleomorphic liposarcoma: a case report and literature review. (PubMed, J Clin Pathol)
The patient underwent complete removal of the tumour without the use of radiotherapy or chemotherapy. No recurrence was observed during the follow-up period of 18 months.
Review • Journal
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TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • TERT (Telomerase Reverse Transcriptase) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • ETV1 (ETS Variant Transcription Factor 1) • DDIT3 (DNA-damage-inducible transcript 3) • CREB5 (CAMP Responsive Element Binding Protein 5)
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TP53 mutation • CDK4 amplification
4ms
Dalpiciclib combined with camrelizumab in Treating Patients with Recurrent and/or Metastatic Mucosal Melanoma of Head and Neck Harboring CDK4 Amplification (ChiCTR2300073726)
P2, N=30, Not yet recruiting, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine; Shanghai Ninth People's Hospital, Shanghai Jiaotong University Scho
New P2 trial
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CDK4 (Cyclin-dependent kinase 4)
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CDK4 amplification
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AiRuiKa (camrelizumab) • AiRuiKang (dalpiciclib)
4ms
Genetic alterations that deregulate RB and PDGFRA signaling pathways drive tumor progression in IDH2-mutant astrocytoma. (PubMed, Acta Neuropathol Commun)
These findings suggest that gene alterations that activate retinoblastoma (RB) signaling pathways and PDGFR may drive tumor progression and xenograft formation in IDH2-mutant astrocytoma, which is equivalent to progressive IDH1-mutant astrocytoma. Also, our findings suggest that these genomic alterations may represent therapeutic targets in IDH2-mutant astrocytoma.
Journal
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TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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TP53 mutation • IDH1 mutation • IDH2 mutation • CDKN2A deletion • CDKN2A mutation • CDK4 amplification • IDH2 mutation + TP53 mutation
4ms
KDM2B-Rearranged Soft-Tissue Sarcomas Expand the Concept of BCOR-Associated Sarcoma. (PubMed, Mod Pathol)
This may be related to the known molecular relationship between KDM2B and BCOR in the polycomb repressive complex 1.1. Immunohistochemical analysis of KDM2B is a potentially valuable diagnostic tool for BCOR-associated sarcomas, including those with KDM2B rearrangement.
Journal
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CREBBP (CREB binding protein) • BCOR (BCL6 Corepressor) • NUTM2B (NUT Family Member 2B) • DUX4 (Double Homeobox 4) • SATB2 (SATB Homeobox 2)
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CDK4 amplification
5ms
Clinicopathologic Analysis and Molecular Profiling of Ovarian Steroid Cell Tumors. (PubMed, Am J Surg Pathol)
Genomic alterations are infrequent but occur in malignant SCTs as well as a subset of benign SCTs. Molecular analysis of additional malignant SCTs is necessary to identify recurring and/or potentially actionable targets.
Journal
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TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase) • BAP1 (BRCA1 Associated Protein 1) • CDK4 (Cyclin-dependent kinase 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • ATRX (ATRX Chromatin Remodeler) • CASP10 (Caspase 10)
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TP53 mutation • BAP1 mutation • CDK4 amplification • CTNNB1 mutation
5ms
Combination of PARP inhibitor and CDK4/6 inhibitor modulates cGAS/STING-dependent therapy-induced senescence and provides "one-two punch" opportunity with anti-PD-L1 therapy in colorectal cancer. (PubMed, Cancer Sci)
Collectively, we elucidated the synergistic antitumor and immunomodulatory mechanisms of the talazoparib-palbociclib combination. Further combination with PD-L1 antibody might be a promising "one-two punch" therapeutic strategy for colorectal cancer patients.
Journal • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CD8 (cluster of differentiation 8) • CDK4 (Cyclin-dependent kinase 4) • STING (stimulator of interferon response cGAMP interactor 1)
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BRCA2 mutation • BRCA1 mutation • CDK4 amplification
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Ibrance (palbociclib) • Talzenna (talazoparib)
5ms
Sarcoma care in the era of precision medicine. (PubMed, J Intern Med)
It is reasonable to believe that most sarcoma treatment centers will increase the use of massive-parallel sequencing soon. We conclude that the context in which the genetic findings are interpreted is of importance, and the interpretation of genomic findings requires considering tumor histomorphology.
Review • Journal
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KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • STAT6 (Signal transducer and activator of transcription 6) • NAB2 (NGFI-A Binding Protein 2)
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CDK4 amplification
5ms
Single cell transcriptomics, pharmacokinetics, and pharmacodynamics of combined CDK4/6 and mTOR inhibition in a phase 0 trial of recurrent high-grade glioma (SNO 2023)
This study highlights the value of integrating pharmacokinetics/pharmacodynamics and snRNA data to assess treatment effects in phase 0 surgical tissues. These findings support further development of ribociclib, but not everolimus, for the treatment of glioma patients.
PK/PD data
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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PIK3CA mutation • CDKN2A deletion • CDK4 amplification • IDH wild-type
|
everolimus • Kisqali (ribociclib)
5ms
The value of GLI1 and p16 immunohistochemistry in the premolecular screening for GLI1-altered mesenchymal neoplasms. (PubMed, Virchows Arch)
In conclusion, we confirm that GLI1 IHC represents a good, quick, and cheap helpful screening tool. The inclusion of p16 may aid in pre-screening for potential GLI1-amplified neoplasms and provide insights on which tumors warrant further molecular testing.
Journal
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MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • GLI1 (GLI Family Zinc Finger 1)
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CDK4 amplification
5ms
Osteosarcomas with few chromosomal alterations and/or affecting adults are genetically heterogeneous. (PubMed, Lab Invest)
Due to lack of clinical context and available tissue, we can question the diagnosis only on a genetic basis. Our findings, however, support the notion that osteosarcomas with few chromosomal alterations and/or affecting adults seem genetically distinct from conventional osteosarcomas of children and adolescents.
Journal
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TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
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CDK4 amplification
5ms
Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors (clinicaltrials.gov)
P1/2, N=337, Recruiting, Pfizer | Trial completion date: Feb 2026 --> Sep 2027 | Trial primary completion date: Feb 2026 --> Jul 2026
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1) • CD4 (CD4 Molecule)
|
HER-2 positive • HR positive • HER-2 negative • CCND1 amplification • CDK4 amplification • HR positive + HER-2 negative • HR positive + HER-2 positive
|
enzalutamide capsule • fulvestrant • letrozole • atirmociclib (PF-07220060) • midazolam hydrochloride
5ms
Phase II trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/ CDKN2A. (PubMed, Signal Transduct Target Ther)
Translational research showed a significant correlation between CDK4 mRNA and protein expression. Palbociclib was active in a variety of sarcoma subtypes, selected by CDK4/CDKN2A, and deserves further investigation in the sarcoma context.
P2 data • Journal • Metastases
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
|
CDK4 amplification • CDK4 overexpression
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Ibrance (palbociclib)
5ms
Liposarcoma Involving Serous Fluid Cavities-A Case Series Illustrating Clinical Implications and the Diagnostic Role of Exfoliative Cytology. (PubMed, Int J Surg Pathol)
Lipomatous and dedifferentiated components can be sampled and cytomorphologically identified on effusion fluids of liposarcomas, with sufficient cellularity for immunocytochemistry and molecular testing. Although generally associated with poor prognosis, long disease-free survival with sarcomatous effusion is possible with radical surgery and adjuvant treatment.
Journal • Cytology
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MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
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MDM2 amplification • CDK4 amplification • MDM2 amplification + CDK4 amplification
6ms
TARGETED THERAPY ADAPTED TO TUMOR BIOLOGY IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA OR HEPATOCHOLANGIOCARCINOMA REFRACTORY TO ATEZOLIZUMAB/BEVACIZUMAB (AASLD 2023)
One patient with H-CCK showing CDK4 amplification was treated by Palbociclib, he experienced a partial radiological response during 16 months. Another patient with H-CCK and high HER2 overexpression and a high homologous recombination score was treated by Trastuzumab/Olaparib with had a stable disease at the first imaging evaluation...The remaining six treated patients (6 HCC) harbored a progressive disease including three patients treated by Trametinib, two by Everolimus and one by Olaparib. Molecular based guided therapy is feasible in patients with HCC and H-CCK and progressing under atezolizumab/bevacizumab. Forty five percent received a therapy adapted to a genomic alteration with a clinical benefit in one third of them.
Clinical • PARP Biomarker • PD(L)-1 Biomarker • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • CDK4 (Cyclin-dependent kinase 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • TSC2 (TSC complex subunit 2) • TSC1 (TSC complex subunit 1) • TMEM127 (Transmembrane Protein 127)
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HER-2 overexpression • PIK3CA mutation • CCND1 amplification • CDK4 amplification • TSC1 mutation • FGF19 amplification
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Avastin (bevacizumab) • Herceptin (trastuzumab) • Lynparza (olaparib) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • everolimus
6ms
CDK4/6 Tumor, Abemaciclib, Paclitaxel (clinicaltrials.gov)
P1/2, N=30, Active, not recruiting, Yonsei University | Trial completion date: Aug 2022 --> Aug 2024 | Trial primary completion date: Aug 2022 --> Aug 2024
Trial completion date • Trial primary completion date • Pan tumor
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CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6)
|
CCND1 amplification • CDK4 amplification • CCND1 mutation
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paclitaxel • Verzenio (abemaciclib)
6ms
Study of Ribociclib and Everolimus in HGG and DIPG (clinicaltrials.gov)
P2, N=100, Not yet recruiting, Nationwide Children's Hospital | Trial completion date: Aug 2033 --> Jan 2034 | Initiation date: Aug 2023 --> Jan 2024 | Trial primary completion date: Aug 2027 --> Jan 2028
Trial completion date • Trial initiation date • Trial primary completion date
|
PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CDKN2C (Cyclin Dependent Kinase Inhibitor 2C)
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PIK3CA mutation • PTEN mutation • CDKN2A deletion • PIK3CA amplification • CCND1 amplification • CDK4 amplification • PIK3R1 mutation
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everolimus • Kisqali (ribociclib)
7ms
New P1 trial • Combination therapy • Surgery
|
MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4)
|
CDK4 amplification
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Verzenio (abemaciclib)
7ms
Metastatic Dedifferentiated Liposarcoma With Morphologic Similarity to Well-Differentiated Neuroendocrine Tumor (CAP 2023)
When the patient’s prior dedifferentiated liposarcoma was reviewed, a small focus of the tumor demonstrated a similar round cell morphology (Figure 2.121, C), although most of the dedifferentiated component showed more typical spindle-cell features (Figure 2.121, D). This case highlights a previously unknown and diagnostically misleading presentation of dedifferentiated liposarcoma, adding to the spectrum of potential morphologies this tumor can exhibit.
Metastases
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MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • NCAM1 (Neural cell adhesion molecule 1) • SYP (Synaptophysin)
|
MDM2 amplification • CDK4 amplification
7ms
A threshold for mitotic activity and post-surgical residual volume defines distinct prognostic groups for astrocytoma IDH-mutant. (PubMed, Neuropathol Appl Neurobiol)
Mitotic activity and post-surgical residual volume can be combined to evaluate the prognosis for patients with resected astrocytomas IDH-mutant. Patients with <6 mitoses per 3 mm and a residual volume <1 cm were the best candidates for observational follow-up.
Journal
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler)
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CDKN2A deletion • CDK4 amplification
7ms
Molecular-based targeted therapies in patients with hepatocellular carcinoma and hepato-cholangiocarcinoma refractory to atezolizumab/bevacizumab. (PubMed, J Hepatol)
Molecular-based guided therapy is feasible in patients with HCC/H-CCK progressing under atezolizumab/bevacizumab and may be useful in a small subset of patients.
Journal • PARP Biomarker • PD(L)-1 Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • CDK4 (Cyclin-dependent kinase 4) • TSC2 (TSC complex subunit 2)
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HER-2 overexpression • CDK4 amplification
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Avastin (bevacizumab) • Herceptin (trastuzumab) • Lynparza (olaparib) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • everolimus
7ms
Epithelioid dedifferentiated liposarcoma: A clinicopathological and molecular study of 6 cases. (PubMed, Ann Diagn Pathol)
The study presented herein further highlights the aggressive clinical behavior of this unique tumor type. For patients with advanced disease, CDK4 inhibitor may provide an optional targeted treatment.
Journal
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MDM2 (E3 ubiquitin protein ligase)
|
CDK4 amplification
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)
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CCNE1 overexpression • CDK4 amplification • CCND1 overexpression • CDK4 overexpression • CDK2 overexpression • CDK6 overexpression • CCND2 overexpression • PPP3CA expression
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MI Tumor Seek™
8ms
COMPARISON OF A PATIENT-DERIVED XENOGRAFTS (PDX) OF MYXOID PLEOMORPHIC LIPOSARCOMA (MPL) AND PLEOMORPHIC LIPOSARCOMA (PL) HIGHLIGHTS THE EFFECTIVENESS OF ERIBULIN IN A PDX OF MPL (CTOS 2023)
Antitumor activity of single-agent doxorubicin, ifosfamide, trabectedin, eribulin and selinexor as well as the combination of doxorubicin plus ifosfamide was tested in each model. To the best of our knowledge this is the first PDX model of MPL and this study suggests the potential relevance of eribulin for this disease. In addition, the comparison with a PDX model of PL highlights different response to treatment approaches, such as the first line treatment options for soft tissue sarcomas doxorubicin with or without ifosfamide. Further analyses are ongoing to understand the determinants of eribulin activity in MPL
Clinical
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MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • DDIT3 (DNA-damage-inducible transcript 3)
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CDK4 amplification
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doxorubicin hydrochloride • ifosfamide • Halaven (eribulin mesylate) • Xpovio (selinexor) • Yondelis (trabectedin)
8ms
Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials. (PubMed, Int J Cancer)
In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.
Journal • IO biomarker • Metastases
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3)
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CCND1 amplification • CDK4 amplification
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Ibrance (palbociclib) • Kisqali (ribociclib)
8ms
A comprehensive genomic study of 390 H3F3A-mutant pediatric and adult diffuse high-grade gliomas, CNS WHO grade 4. (PubMed, Acta Neuropathol)
Through our analysis, we were able to identify molecular features characteristic of DMG and DHG. By identifying the recurrent co-mutations including actionable FGFR1 point mutations found in nearly one-third of H3K27M-mutant DMG in young adults, our findings can inform clinical translational studies, patient diagnosis, and clinical trial design.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • CDK6 (Cyclin-dependent kinase 6) • H3-3A (H3.3 Histone A)
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PIK3CA mutation • NF1 mutation • CDKN2A deletion • FGFR1 mutation • CDK4 amplification • PIK3R1 mutation • CDK6 amplification
8ms
ROS1 alterations as a potential driver of gliomas in infant, pediatric, and adult patients. (PubMed, Mod Pathol)
We conclude that ROS1 likely acts as a driver in infant and pediatric gliomas and as a driver or co-driver in adult gliomas. Integrated comprehensive clinical testing might be helpful in identifying such patients for possible targeted therapy.
Journal
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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TP53 mutation • PIK3CA mutation • PTEN mutation • CDKN2A deletion • ROS1 fusion • ROS1 positive • CDK4 amplification • PDGFRA mutation • GOPC-ROS1 fusion • IDH wild-type • MDM2 mutation • PIK3R1 mutation • CDK4 mutation
8ms
A Study of Abemaciclib in Recurrent Glioblastoma (clinicaltrials.gov)
P2; Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2023 --> Jun 2024
Trial completion date • Trial primary completion date
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CDK6 (Cyclin-dependent kinase 6)
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CDKN2A deletion • CDK4 amplification • IDH wild-type • RB1 wild-type
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OncoPanel™ Assay
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Verzenio (abemaciclib)
8ms
Preclinical and ongoing phase I study data of the CHK1 inhibitor BBI-355 in development for patients with oncogene amplification on extrachromosomal DNA (ecDNA) (ESMO 2023)
Conclusions The first ecDNA directed therapy, BBI-355, demonstrated significant anti-tumor activity as a single agent and in combination with targeted therapies in multiple ecDNA+ oncogene amplified tumor models. Clinical testing in patients with oncogene amplification is ongoing.
P1 data • Preclinical
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FGFR2 (Fibroblast growth factor receptor 2) • CHEK1 (Checkpoint kinase 1)
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EGFR wild-type • FGFR2 amplification • CDK4 amplification
8ms
Clinical Impact of Genomic Characterization in Induced Oligometastatic Non-small Cell Lung Cancer (IASLC-WCLC 2023)
Resistance to targeted therapy, ITH, and genomic instability driven by HRD may contribute to the persistence and recurrence of oligometastatic lesions in advanced NSCLC. Increased ITH and HRD events were associated with inferior clinical outcomes. These findings could help to further improve treatment strategies after LCT and after drug resistance in patients with oligometastatic NSCLC.
Clinical • Tumor mutational burden • IO biomarker • Metastases
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BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • EML4 (EMAP Like 4) • HRD (Homologous Recombination Deficiency) • MCL1 (Myeloid cell leukemia 1) • CDK4 (Cyclin-dependent kinase 4) • MUC17 (Mucin 17)
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BRAF V600E • BRAF V600 • MET amplification • EGFR T790M • HRD • CDK4 amplification • MCL1 amplification