CCND1 amplification is a recurring event in breast cancer, occurring most frequently in luminal B-like and HER2-amplified subtypes. A trend toward less favorable outcomes was observed among CCND1-amplified HR-positive, HER2-negative tumors.

23 days ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • CCND1 (Cyclin D1)

HER-2 positive • HR positive • HER-2 amplification • HER-2 negative • CCND1 amplification • HR positive + HER-2 negative • HER-2 amplification + HR-positive

28d

Palbociclib and Pembrolizumab in Central Nervous System Metastases (clinicaltrials.gov)

P2, N=45, Recruiting, Massachusetts General Hospital | N=30 --> 45 | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

28 days ago

Enrollment change • Trial completion date • Trial primary completion date

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3)

CCNE1 amplification • CCND1 amplification • CDK4 amplification

Keytruda (pembrolizumab) • Ibrance (palbociclib)

2ms

Point mutations (PM), gene amplifications (GA) and variants of unknown significance (VUS) detected by next-generation sequencing (NGS) in a real-world sample of metastatic breast cancer (MBC) (SABCS 2024)

NGS of real-world patients reveals a broad spectrum of genomic abnormalities in MBC. TP53 and PIK3CA associate with TNBC and luminal MBC, respectively. Mutations in tumor suppressors are mostly distinct since there are many ways to induce loss-of-function.

2 months ago

Clinical • Real-world evidence • Next-generation sequencing • MSi-H Biomarker • Real-world • Metastases

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • KMT2D (Lysine Methyltransferase 2D) • CDK12 (Cyclin dependent kinase 12) • CDH1 (Cadherin 1) • FGF4 (Fibroblast growth factor 4) • AURKA (Aurora kinase A) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • GNAS (GNAS Complex Locus) • CCND2 (Cyclin D2) • RAD21 (RAD21 Cohesin Complex Component) • KDM5A (Lysine Demethylase 5A) • ZNF217 (Zinc Finger Protein 217) • FGF23 (Fibroblast Growth Factor 23) • GATA3 (GATA binding protein 3) • ZNF703 (Zinc Finger Protein 703)

TP53 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • HER-2 expression • PIK3CA H1047R • FGFR1 amplification • CCND1 amplification • FGF3 amplification

Guardant360® CDx

2ms

The interplay of mutagenesis and ecDNA shapes urothelial cancer evolution. (PubMed, Nature)

Experimental modelling of CCND1 ecDNA confirmed its role as a driver of treatment resistance. Our findings define fundamental mechanisms that drive urothelial cancer evolution and have important therapeutic implications.

2 months ago

Journal

CCND1 (Cyclin D1)

CCND1 amplification

3ms

Gastric-type extremely well-differentiated adenocarcinoma of the stomach: A rare tumor with diagnostic difficulties and high inter-observer variation in endoscopic pinch biopsies. (PubMed, Pathol Res Pract)

In conclusion, it is challenging to diagnose EWDGA using biopsy specimens. Recognizing and addressing this rare entity will increase diagnostic accuracy to ensure the early diagnosis of cancer.

3 months ago

Journal • Biopsy

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • CCND1 (Cyclin D1) • MDM2 (E3 ubiquitin protein ligase)

TP53 mutation • KRAS mutation • BRAF mutation • STK11 mutation • CCND1 amplification • TP53 overexpression

3ms

Study of Ribociclib and Everolimus in HGG and DIPG (clinicaltrials.gov)

P2, N=100, Recruiting, Nationwide Children's Hospital | Not yet recruiting --> Recruiting

3 months ago

Enrollment open

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)

PIK3CA mutation • PTEN mutation • CDKN2A deletion • PIK3CA amplification • CCND1 amplification • CDK4 amplification • PIK3R1 mutation

everolimus • Kisqali (ribociclib)

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.

3 months ago

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

3ms

Circulating tumor DNA (ctDNA) as a biomarker of response to therapy in advanced Hepatocellular carcinoma treated with Nivolumab. (PubMed, Cancer Biomark)

ctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.

3 months ago

Journal • BRCA Biomarker • PD(L)-1 Biomarker • Circulating tumor DNA • Metastases

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • CCND1 (Cyclin D1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

BRCA1 mutation • PIK3CA mutation • KIT mutation • CCND1 amplification • CTNNB1 mutation

Opdivo (nivolumab)

3ms

p16 Immunohistochemical Patterns in Triple-Negative Breast Cancer: Clinical and Genomic Similarities of the p16 Diffuse Pattern to pRB Deficiency. (PubMed, Pathobiology)

CCND1 amplification was identified in five cases, all with the negative/mosaic pattern In TNBC, the diffuse p16 pattern shows clinical and genomic similarities to pRB-deficient tumors, suggesting shared characteristics. This suggests that p16 IHC testing may provide new therapeutic approaches, underscoring its potential clinical importance.

3 months ago

Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • HRD (Homologous Recombination Deficiency) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1)

PIK3CA mutation • HRD • CCND1 amplification

8ms

Study of Ribociclib and Everolimus in HGG and DIPG (clinicaltrials.gov)

P2, N=100, Not yet recruiting, Nationwide Children's Hospital | Trial completion date: Jan 2034 --> May 2034 | Initiation date: Jan 2024 --> May 2024 | Trial primary completion date: Jan 2028 --> May 2028

8 months ago

Trial completion date • Trial initiation date • Trial primary completion date

PIK3CA mutation • PTEN mutation • CDKN2A deletion • PIK3CA amplification • CCND1 amplification • CDK4 amplification • PIK3R1 mutation

everolimus • Kisqali (ribociclib)

9ms

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: Oct 2027 --> May 2028 | Trial primary completion date: Aug 2026 --> Mar 2027

9 months ago

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 • PTEN mutation + HR positive

Xtandi (enzalutamide) • fulvestrant • letrozole • atirmociclib (PF-07220060) • midazolam hydrochloride

9ms

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

9 months ago

Trial completion date

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

CDKN2A deletion • CCND1 amplification • CDK4 amplification

Kisqali (ribociclib)

10ms

Genomic Variability Within Intrinsic Subtypes of Advanced Breast Cancer (USCAP 2024)

There is a great genomic variability in each intrinsic subtype of advanced BC, with apparently no genomic pattern correlating with each phenotype. Although a transcriptomic test (Prosigna) can help in the classification of the tumors, NGS sequencing with an extended panel allows identifying genetic variants that might benefit the patient with a targeted therapy i a significant percentage of cases.

10 months ago

BRCA Biomarker • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • SF3B1 (Splicing Factor 3b Subunit 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3)

HER-2 negative • PTEN mutation • MYC amplification • CCND1 amplification • AKT1 mutation • TP53 amplification

Prosigna™ Breast Cancer Prognostic Gene Signature Assay

10ms

Study of the CDK4/6 Inhibitor Abemaciclib in Solid Tumors Harboring Genetic Alterations in Genes Encoding D-type Cyclins or Amplification of CDK4 or CDK6 (clinicaltrials.gov)

P2; Trial primary completion date: Jun 2024 --> Dec 2024

10 months ago

Trial primary completion date

CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6)

CCND1 amplification • CDK4 amplification • CCND1 mutation

OncoPanel™ Assay

Verzenio (abemaciclib)

11ms

Multiparametric prognostic score in early HR+/HER2- breast cancer: Impact of recurrence score, clinical-pathological factors, gene mutations and histology (YIR 2024)

Use of RS in combination with further clinical and genetic factors improves prognostic ability; however, there is no treatment-independent prognostic model for HR+ HER2- EBC pts. For the first time, we have shown worse prognosis of the ILC high-risk subgroup, associated with distinct biological features.

11 months ago

Clinical

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CCND1 (Cyclin D1) • CDH1 (Cadherin 1)

HER-2 negative • CCND1 amplification • CDH1 mutation • PGR expression

Oncotype DX Breast Recurrence Score®Test

12ms

MegaMOST: A Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/Characteristics in Advanced / Metastatic Tumors. (clinicaltrials.gov)

P2, N=425, Recruiting, Centre Leon Berard

12 months ago

Trial completion date • Trial primary completion date • Metastases

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • AXL (AXL Receptor Tyrosine Kinase) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SMAD4 (SMAD family member 4) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • FLT1 (Fms-related tyrosine kinase 1) • CDK6 (Cyclin-dependent kinase 6) • CCND3 (Cyclin D3) • TYRO3 (TYRO3 Protein Tyrosine Kinase) • NTRK (Neurotrophic receptor tyrosine kinase)

KRAS mutation • EGFR mutation • BRAF mutation • NRAS mutation • BRAF V600 • FGFR1 amplification • CDKN2A deletion • HRAS mutation • PTPN11 mutation • CCND1 amplification • KRAS amplification • BRAF amplification

Mekinist (trametinib) • Tafinlar (dabrafenib) • Alecensa (alectinib) • Cabometyx (cabozantinib tablet) • Stivarga (regorafenib) • Kisqali (ribociclib) • Ayvakit (avapritinib) • siremadlin (HDM201)

1year

The Molecular, Immunologic, and Clinicodemographic Landscape of MYC-Amplified Advanced Prostate Cancer. (PubMed, Clin Genitourin Cancer)

MYC defines a biologically distinct subset of PCa patients and is characterized with multiple proxies of advanced disease. These data suggest that MYC may be prognostic; independent cohorts are needed to validate these findings.

1 year ago

Journal • PD(L)-1 Biomarker • IO biomarker • Metastases

PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • FGFR1 (Fibroblast growth factor receptor 1) • CCND1 (Cyclin D1) • FGF3 (Fibroblast growth factor 3) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • RAD21 (RAD21 Cohesin Complex Component) • ZNF703 (Zinc Finger Protein 703)

PD-L1 expression • MSI-H/dMMR • MYC amplification • CCND1 amplification

1year

ORAOV1, CCND1, and MIR548K are the driver oncogenes of the 11q13 amplicon in squamous cell carcinoma. (PubMed, Mol Cancer Res)

Thus, the 11q13 amplicon drives SCC through at least three independent genetic elements and suggests therapeutic targets for this morbid and lethal disease. Implications: This work demonstrates novel mechanisms and ways to target these mechanisms underlying the most common amplification in squamous cell carcinoma, one of the most prevalent and deadly forms of human cancer.

1 year ago

Journal

RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • RRM2 (Ribonucleotide Reductase Regulatory Subunit M2)

CCND1 amplification

1year

Results of Comprehensive Genomic Profiling of Metastatic Breast Cancer Patients at a Single Institute in Japan (SABCS 2023)

Three HER2-negative patients were prescribed anti-HER2 therapy for ERBB2 amplification, one patient was prescribed entrectinib for NTRK fusion, and three patients participated in clinical trial for ERBB2 mutation and FGFR1 rearrangement. If ESCAT ranking beyond I/II and recommended therapy from FoundationOne report (e.g Abemaciclib for CCND1 amplification, Everolimus for PTEN loss)are added, 64 pts (60.1%) were considered these treatments, and 19 pts (18.1%) actually received these treatment...Low accessibility of ESCAT ranking I/II MT may be because, in Japan, CGP testing is available only for patients who have completed or are expected to complete standard therapy. Early use of CGP testing and an increase in clinical trials will be desirable in Japan.

1 year ago

Clinical • Metastases

PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • CCND1 (Cyclin D1) • NTRK (Neurotrophic receptor tyrosine kinase)

HER-2 amplification • HER-2 negative • FGFR1 mutation • CCND1 amplification • FGFR1 fusion • FGFR1 rearrangement • NTRK fusion

FoundationOne® CDx • FoundationOne® Liquid CDx • OncoGuide™ NCC Oncopanel System

Rozlytrek (entrectinib) • everolimus • Verzenio (abemaciclib)

1year

Baseline genomic alterations and the activity of lasofoxifene (LAS) plus abemaciclib (Abema) in patients with ER+/HER2- metastatic breast cancer (mBC): the ELAINE 2 study (SABCS 2023)

Of the 29 patients (median age 60 yrs) enrolled, mutations in ESR1 were identified in 26 by Guardant360; all these 26 patients had received prior CDK4/6i, 21 (81%) prior fulvestrant, and 12 (46%) prior chemotherapy for mBC. Using Guardant360 ctDNA profiling from patients in ELAINE 2, we demonstrate that other baseline genomic alterations are frequently detected concurrently with mESR1 in the endocrine resistant setting, but without apparent compromise on the efficacy of LAS plus Abema. These results should be interpreted with caution considering the small numbers of patients and the exploratory nature of the analysis. The ELAINE 2 study suggests the potential of LAS plus Abema for treating ESR1-mutated, ER+/HER2- mBC in the post-CDK4/6i setting.

1 year ago

Clinical • Metastases

TP53 mutation • ER positive • HER-2 negative • PIK3CA mutation • FGFR1 amplification • ER mutation • CCND1 amplification • ESR1 mutation • ER positive + HER-2 negative • ER positive + ESR1 mutation + CCND1 amplification • ER positive + ESR1 mutation + FGFR1 amplification • ER positive + ESR1 mutation + PIK3CA mutation • ER positive + ESR1 mutation + TP53 mutation • CDK4 mutation

Guardant360® CDx

Verzenio (abemaciclib) • fulvestrant • Fablyn (lasofoxifene)

1year

Somatic mutations of a multigene panel in Chinese HER2-positive patients undergoing neoadjuvant therapy and impact on prognosis based on TP53 status:a single-institution retrospective cohort (SABCS 2023)

Furthermore, TP53 mutations had significant prognostic importance in HER2-positive BC patients with HR-negative (HR=3.712, P=0.0266), pCR (HR=6.253, P=0.0268) and who received trastuzumab-only targeted therapy (HR=4.145, P=0.0105). Regard to diverse hormone receptor status or neoadjuvant efficacy, the genetic mutation maps of Chinese HER2+ patients receiving NAT are disparate. Our study found that TP53 mutations have significant prognostic value in patients with NAT for HER2-positive BC and patients benefit differently depending on HR status, neoadjuvant regimens and response.

1 year ago

Retrospective data

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CCND1 (Cyclin D1) • KMT2C (Lysine Methyltransferase 2C) • GATA3 (GATA binding protein 3)

HER-2 positive • TP53 mutation • HER-2 mutation • CCND1 amplification • GATA3 mutation

Herceptin (trastuzumab)

1year

Examining Rare Genitourinary Cancers for Genetic Biomarkers to Explore Potential Targeted Therapy Options (AMP 2023)

Data from this small cohort of rare tumors suggest that SCNC and SqCB exhibit common driver/targetable mutations seen in other hematologic and solid tumors that might represent new therapeutic targets in these rare tumor types. Our identification of mutations unique to different histologies in the same tumor argues for independent sequencing of different histologies to broaden the search for targetable mutations.

1 year ago

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • CCND1 (Cyclin D1)

TP53 mutation • PIK3CA mutation • NF1 mutation • FGFR3 mutation • CDKN2A mutation • CCND1 amplification • FGFR3 fusion • TERT mutation • TERT promoter mutation

TruSight Tumor 170 Assay

1year

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

1 year ago

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

Xtandi (enzalutamide) • fulvestrant • letrozole • atirmociclib (PF-07220060) • midazolam hydrochloride

1year

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.

1 year ago

Clinical • PARP Biomarker • PD(L)-1 Biomarker • Metastases

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)

HER-2 overexpression • PIK3CA mutation • CCND1 amplification • CDK4 amplification • TSC1 mutation • FGF19 amplification

Avastin (bevacizumab) • Herceptin (trastuzumab) • Lynparza (olaparib) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Ibrance (palbociclib) • everolimus

1year

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

1 year ago

Trial completion date • Trial primary completion date • Pan tumor

CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6)

CCND1 amplification • CDK4 amplification • CCND1 mutation

paclitaxel • Verzenio (abemaciclib)

1year

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

1 year ago

Trial completion date • Trial initiation date • Trial primary completion date

PIK3CA mutation • PTEN mutation • CDKN2A deletion • PIK3CA amplification • CCND1 amplification • CDK4 amplification • PIK3R1 mutation

everolimus • Kisqali (ribociclib)

over1year

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.

over 1 year ago

Journal • IO biomarker • Metastases

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)

CCND1 amplification • CDK4 amplification

Ibrance (palbociclib) • Kisqali (ribociclib)

over1year

Prognostic significance of CCND1 amplification/overexpression in smoking patients with esophageal squamous cell carcinoma. (PubMed, Cancer Genet)

Further univariate and multivariate analysis revealed CCND1 amplification was independently poorer prognostic factor in smoking patients, which was not found in non-smoking patients. Smokers with CCND1 amplification or cyclinD1 overexpression have poorer survival, which help us to identify distinct groups of patients with apparently poorer outcome and would enable appropriate follow-up and treatment strategies.

over 1 year ago

Journal

CCND1 (Cyclin D1)

CCND1 amplification • CCND1 overexpression

over1year

CCND1-associated ceRNA network reveal the critical pathway of TPRG1-AS1-hsa-miR-363-3p-MYO1B as a prognostic marker for head and neck squamous cell carcinoma. (PubMed, Sci Rep)

RT-qPCR validated bioinformatic predictions of gene expression in vitro cell lines. In conclusion, we found a CCND1-related ceRNA network and identified the novel TPRG1-AS1-hsa-miR-363-3p-MYO1B pathway as a possible HNSC diagnostic biomarker and therapeutic target.

over 1 year ago

Journal

CCND1 (Cyclin D1) • MIR363 (MicroRNA 363)

CCND1 amplification • CCND1 expression

over1year

Sex-based differences in genomic alterations and biomarkers in anal squamous cell carcinoma (ASCC) (ESMO 2023)

Conclusions The higher incidence of HPV positivity in F compared to M remains the main hypothesis to justify the better prognosis of ASCC in women. A large proportion of PD-L1+ and TMB-High (âˆ¼70%), PIK3CA alterations (âˆ¼30%) and BRCA1/2 gene alteration (5%) may predict response to possible new therapeutic approaches for pts with ASCC like immunotherapy, targeted tyrosine kinase inhibitors, platinum chemotherapy and PARP inhibitors.

over 1 year ago

Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • BRCA Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • KMT2D (Lysine Methyltransferase 2D) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FGF3 (Fibroblast growth factor 3) • CREBBP (CREB binding protein) • FGF4 (Fibroblast growth factor 4)

PD-L1 expression • BRCA2 mutation • BRCA1 mutation • TMB-H • CCND1 amplification • BRCA1 mutation + BRCA2 mutation

FoundationOne® CDx

over1year

Multiparametric prognostic score in early HR+/HER2- breast cancer: Impact of recurrence score, clinical-pathological factors, gene mutations and histology (ESMO 2023)

Conclusions Use of RS in combination with further clinical and genetic factors improves prognostic ability; however, there is no treatment-independent prognostic model for HR+ HER2- EBC pts. For the first time, we have shown worse prognosis of the ILC high-risk subgroup, associated with distinct biological features.

over 1 year ago

Late-breaking abstract • Clinical

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CCND1 (Cyclin D1) • CDH1 (Cadherin 1)

HER-2 negative • CCND1 amplification • CDH1 mutation • PGR expression

Oncotype DX Breast Recurrence Score®Test

over1year

Aumolertinib Plus Anlotinib in Advanced NSCLC with Brain Metastasis: A Single-arm, Phase II Study (IASLC-WCLC 2023)

In addition, EGFR-TKIs combined with bevacizumab can further improve the efficacy, as reported in study JO25567 and NEJ026. Aumolertinib plus anlotinib showed preliminary efficacy as first-line therapy in EGFR-mutant NSCLC patients with brain metastases. The initial subgroup results may demonstrated superior activity of aumolertinib plus anlotinib in patients with multiple intracranial metastases or EGFR 19Del positive. And although with comutations, NSCLC patients with brain metastasis can still benefit from aumolertinib plus anlotinib.

over 1 year ago

P2 data • Metastases

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • CCND1 (Cyclin D1)

TP53 mutation • EGFR mutation • PIK3CA mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • EGFR amplification • PIK3CA amplification • CCND1 amplification • EGFR positive • TP53 amplification

Avastin (bevacizumab) • Focus V (anlotinib) • Ameile (aumolertinib)

over1year

An updated literature on BRAF inhibitors (2018-2023). (PubMed, Mol Divers)

The development of BRAF inhibitors to overcome the persistent limitation such as resistance, mutation, and adverse effects of drugs. In depth description about different heterocyclic scaffolds (quinoline, imidazole, pyridine, triazole, pyrrole etc.) as BRAF inhibitors from the last five years (2018-2023) highlighting the structure-activity relationship, mechanistic study, and molecular docking studies.

over 1 year ago

Review • Journal

PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1) • CCND1 (Cyclin D1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • RAC1 (Rac Family Small GTPase 1)

BRAF mutation • NF1 mutation • CCND1 amplification • BRAF amplification

over1year

Study of the CDK4/6 Inhibitor Abemaciclib in Solid Tumors Harboring Genetic Alterations in Genes Encoding D-type Cyclins or Amplification of CDK4 or CDK6 (clinicaltrials.gov)

P2; Trial primary completion date: Jun 2023 --> Jun 2024

over 1 year ago

Trial primary completion date

CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6)

CCND1 amplification • CDK4 amplification • CCND1 mutation

OncoPanel™ Assay

Verzenio (abemaciclib)

over1year

ERα-associated translocations underlie oncogene amplifications in breast cancer. (PubMed, Nature)

A pan-cancer analysis reveals tissue-specific biases in mechanisms initiating focal amplifications, with the breakage-fusion-bridge cycle prevalent in some and the translocation-bridge amplification in others, probably owing to the different timing of DNA break repair. Our results identify a common mode of oncogene amplification and propose oestrogen as its mechanistic origin in breast cancer.

over 1 year ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CCND1 (Cyclin D1)

HER-2 amplification • CCND1 amplification

over1year

Clinical Application of Liquid Biopsy across Pan- Cancer: 4baseCare's Experience Using TarGT Indiegene- Liquid Biopsy NGS Panel (AMP Europe 2023)

The MRD estimation was evident in a breast cancer patient with ERBB2 amplification detected while the patient was on maintenance trastuzumab... This pan- cancer pilot study using the TarGT Indiegene Liquid Biopsy Panel supports the hypothesis that molecular information obtained from liquid biopsy can play a significant role in clinical decision-making, in addition to tissue mutation profiling. The results of this study demonstrate the potential clinical utility of this liquid biopsy panel in identifying actionable genomic alterations in patients with advanced stage cancer. These findings suggest that liquid biopsy has the potential to complement tissue biopsy and provide important molecular information to inform personalized treatment decisions for patients with cancer.

over 1 year ago

Clinical • Liquid biopsy • Next-generation sequencing • Biopsy

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CCND1 (Cyclin D1) • FGF3 (Fibroblast growth factor 3) • BICC1 (BicC Family RNA Binding Protein 1)

HER-2 amplification • PIK3CA mutation • FGFR2 fusion • CCND1 amplification • FGF3 amplification

Herceptin (trastuzumab)

over1year

Molecular Landscape of Small-Cell and Large-Cell Neuroendocrine Carcinomas of the Gastroenteropancreatic System (Selected for Oral Presentation, O-01-02) (AMP Europe 2023)

The findings provide insight into the pathogenesis of GEP- NECs and highlight limited similarities to SCLC. Despite the paucity of data about the molecular drivers associated with GEP-NECs, a high fraction of targetable alterations (46% in our cohort) indicates a high potential for better-personalized treatments.

over 1 year ago

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • 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) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • APC (APC Regulator Of WNT Signaling Pathway)

TP53 mutation • BRAF mutation • HER-2 amplification • PIK3CA mutation • HER-2 mutation • APC mutation • CCND1 amplification • CDK4 amplification • AKT1 mutation

FoundationOne® CDx

over1year

Integrated genomic analysis refines molecular classifications of hepatocellular carcinoma based on a large-scale cohort of 529 samples (EACR 2023)

Another subgroup was defined by both CTNNB1ex3 and TP53 mutations, which presented mixed features of CTNNB1ex3 HCC and TP53-mut HCC. In clinicopathological and genomic level, this subgroup presented the characteristics of TP53-mut HCCs with an enrichment of HBV infection, higher Edmonson III-IV grade and CCND1-FGF19 amplification, more copy-number events and high proportion of whole-genome duplication and was associated with poor prognosis, while in the transcriptomic level, CTNNB1ex3; TP53 HCC clustered with CTNNB1ex3 HCCs.ConclusionWe refined the molecular classifications of HCC, which may be useful for therapeutic strategy.

over 1 year ago

IO biomarker • Omic analysis

TP53 (Tumor protein P53) • CCND1 (Cyclin D1) • BAP1 (BRCA1 Associated Protein 1) • FGF19 (Fibroblast growth factor 19) • AXIN1 (Axin 1) • IRF2 (Interferon Regulatory Factor 2) • HNF1A (HNF1 Homeobox A)

TP53 mutation • CCND1 amplification • FGF19 amplification

over1year

Prognostic Values of Gene Copy Number Alterations in Prostate Cancer. (PubMed, Genes (Basel))

The best model of 7/52 genetic CNAs, which included the SPOP alteration, SPP1 alteration, CCND1 amplification, PTEN deletion, CDKN1B deletion, PARP8 deletion, and NKX3.1 deletion, stratified the PCa cases into a localised and advanced disease with an accuracy of 70.0%, sensitivity of 85.4%, specificity of 44.9%, positive predictive value of 71.67%, and negative predictive value of 65.35%. This study validated prognostic gene level CNAs identified in previous studies, as well as identified new genetic markers with CNAs that could potentially impact risk stratification in PCa.

over 1 year ago

Journal • PARP Biomarker

PTEN (Phosphatase and tensin homolog) • CCND1 (Cyclin D1) • SPP1 (Secreted Phosphoprotein 1) • SPOP (Speckle Type BTB/POZ Protein) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • NKX3-1 (NK3 homeobox 1) • PARP8 (Poly(ADP-Ribose) Polymerase Family Member 8)

PTEN deletion • CCND1 amplification

over1year

Identification of BRAF, CCND1, and MYC mutations in a patient with multiple primary malignant tumors: a case report and review of the literature. (PubMed, World J Surg Oncol)

This is the first reported case of a patient with the co-existence of MM, PTC and ccRCC undergoing chemotherapy with a favorable prognosis. Herein, we suggest that such a combination may be non-random, as for mutation of BRAF might account for the co-occurrence of PTC and MM, while mutations of CCND1 and MYC cause the coexistence of MM and ccRCC. This finding may provide valuable guidance on the diagnosis and treatment of such disease, as well as the prevention of developing a second or third tumor for patients with a single primary.

over 1 year ago

Review • Journal

BRAF (B-raf proto-oncogene) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CCND1 (Cyclin D1)

BRAF mutation • CCND1 amplification • MYC mutation • CCND1 mutation