News - CCNE1 elevation

almost2years

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study. (PubMed, Cancer)

This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.

almost 2 years ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1)

CCNE1 amplification • CCNE1 overexpression • CCNE1 elevation

over2years

CCNE1 is a potential target of Metformin for tumor suppression of ovarian high-grade serous carcinoma. (PubMed, Cell Cycle)

Furthermore, molecular simulation docking showed that Metformin may bind to CCNE1 protein, suggesting that CCNE1 could be a potential target for Metformin. Our data revealed that Metformin has antitumor effects on ovarian cancer and CCNE1 could be a potential target for Metformin.

over 2 years ago

Journal

CCNE1 (Cyclin E1)

CCNE1 overexpression • CCNE1 expression • CCNE1 elevation

metformin

over2years

Role of Genetic Variations in CDK2, CCNE1 and p27 in Prostate Cancer. (PubMed, Cancer Genomics Proteomics)

Polymorphisms CDK2 rs2069408, CCNE1 rs997669 and p27 rs2066827 have no significant impact on prostate cancer risk nor on the gene and protein expression of CDK2, CCNE1 and p27, although high CCNE1 expression was significantly associated with a higher tumour grade in patients with prostate cancer.

over 2 years ago

Journal

CCNE1 (Cyclin E1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CDK2 (Cyclin-dependent kinase 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CDKN1B (Cyclin dependent kinase inhibitor 1B)

CCNE1 overexpression • CCNE1 expression • CCNE1 elevation • CDK2 expression • CDKN1B expression

3years

Overlapping molecular features (proliferation, immune signatures and TP53 mutations) associated with palbociclib resistance inER+HER2- primary breast cancer (SABCS 2021)

The PALLET phase II randomized neoadjuvant trial of letrozole (LET) ± palbociclib (PALBO) in postmenopausal ER+HER2- primary breast cancer showed that suppression of proliferation as measured by Ki67 was significantly greater with addition of PALBO to LET but did not result in all patients achieving complete cell-cycle arrest, indicating intrinsic resistance in some patients. We observe, confirming previous studies, an association of CDK4/6 inhibitor resistance, high expression of CCNE1 and genes related to interferon gamma signalling. We show that there is an overlap between resistance mechanisms and TP53 mutations. However, ER+HER2- patients with TP53 mutations may still benefit from PALBO adding to suppression of proliferation compared to LET-only treatment.

3 years ago

PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1) • IFNG (Interferon, gamma) • IDO1 (Indoleamine 2,3-dioxygenase 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)

TP53 mutation • ER positive • HER-2 negative • CCNE1 overexpression • RB1 expression • MAP3K1 mutation • CCNE1 expression • CCNE1 elevation

Ibrance (palbociclib) • letrozole

3years

Biomarkers of response and resistance to palbociclib plus letrozole in patients with ER+/HER2- breast cancer. (PubMed, Clin Cancer Res)

High CCNE1 levels were confirmed as a biomarker of resistance to letrozole+palbociclib. Ki67 recovery within 3-9 days of discontinuing palbociclib indicates incomplete suppression of proliferation during the "off" week of its schedule.

3 years ago

Clinical • Journal • PARP Biomarker

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • PARP1 (Poly(ADP-Ribose) Polymerase 1)

HER-2 negative • ER mutation • CCNE1 elevation

Ibrance (palbociclib) • letrozole

3years

Genomic Profiling in Early Stage ER Positive Breast Cancers/Precision Medicine (SABCS 2021)

We have compared several of these in postmenopausal patients treated with anastrozole or tamoxifen in the ATAC trial, including OncotypeDX (ODX), Prosigna (PAM50) and EndoPredict (EP). Mutation of TP53 was strongly associated with Ki67 poor response. RNAseq profiling of patients treated with palbociclb as well as letrozole revealed high CCNE1 expression as associated with endocrine resistance.

3 years ago

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • IFNG (Interferon, gamma) • IL6 (Interleukin 6)

TP53 mutation • ER positive • CCNE1 overexpression • CCNE1 expression • CCNE1 elevation

Prosigna™ Breast Cancer Prognostic Gene Signature Assay • EndoPredict® • Oncotype DX Breast Recurrence Score®Test

tamoxifen • letrozole • anastrozole

over3years

[VIRTUAL] CCNE1 mRNA and cyclin E1 protein expression as predictive biomarkers for efficacy of palbociclib plus fulvestrant versus capecitabine in the phase III PEARL study. (ASCO 2021)

High tumor CCNE1 mRNA expression identified patients with relative resistance to palbociclib plus fulvestrant, validating prior observations although without statistical significance for interaction . Assessment of Cyclin E1 protein expression did not show predictive value . Investigation treatments to enhance CDK4/6 inhibitor efficacy in tumors with high CCNE1 expression is warranted.

over 3 years ago

P3 data • Clinical

HER-2 (Human epidermal growth factor receptor 2) • CCNE1 (Cyclin E1)

HR positive • HER-2 negative • CCNE1 overexpression • CCNE1 expression • CCNE1 elevation

HTG EdgeSeq Oncology Biomarker Panel (OBP) • HTG EdgeSeq Precision Immuno-Oncology Panel

Ibrance (palbociclib) • capecitabine • fulvestrant