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BIOMARKER:

CCNE1 amplification

i
Other names: CCNE1, CCNE, Cyclin E1
Entrez ID:
Related biomarkers:
1d
Targeted and shallow whole genome sequencing identifies therapeutic opportunities in p53abn endometrial cancers. (PubMed, Clin Cancer Res)
sWGS and targeted sequencing identified therapeutic opportunities in 75% of p53abn EC patients. Further research is needed to determine the efficacy of treatments targeting these identified pathways within p53abn ECs.
Journal • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • HRD (Homologous Recombination Deficiency) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
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TP53 mutation • BRCA2 mutation • BRCA1 mutation • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • HER-2 mutation • HRD • MYC amplification • CCNE1 amplification • HRD + BRCA1 mutation • HRD signature
23d
Characterization of whole genome duplication in a genomic cohort of over 14000 cell free DNA samples (AACR 2024)
WGD was detected in 41% of samples with greater than 10% tumor fraction in cell-free DNA across three cancer types. While this represents a substantial percentage of advanced cancers, more research needs to be done regarding the impact of these events on clinical outcomes and treatment response. Additionally, co-occurrence of these events with other advanced cancer biomarkers such as microsatellite instability or homologous recombination deficiency was not reported.
Cell-free DNA
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TP53 (Tumor protein P53) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1) • WRN (WRN RecQ Like Helicase)
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TP53 mutation • HRD • CCNE1 amplification • RB1 deletion
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GuardantOMNI
23d
A Highly Anticipated Selective Therapeutic Agent against CDK2: INX-315. (PubMed, Cancer Discov)
This agent shows promise in CCNE1-amplified cancers and in CDK4/6 inhibitor-resistant breast cancers. See related article by Dietrich et al., p. 446 (8).
Journal
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CCNE1 (Cyclin E1) • CDK2 (Cyclin-dependent kinase 2)
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CCNE1 amplification
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INX-315
2ms
Discovery of Novel Antitumor Small-Molecule Agent with Dual Action of CDK2/p-RB and MDM2/p53. (PubMed, Molecules)
The results of the druggability evaluation showed that III-13 was characterized by low bioavailability and poor membrane permeability when orally administered, suggesting the necessity of further structural modifications. Therefore, this study provided a lead compound for antitumor drugs, especially those against CCNE1-amplified tumor proliferation.
Journal
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CCNE1 (Cyclin E1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • CDK2 (Cyclin-dependent kinase 2)
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CCNE1 amplification • CCNE1 overexpression
2ms
Discovery of (4-Pyrazolyl)-2-aminopyrimidines as Potent and Selective Inhibitors of Cyclin-Dependent Kinase 2. (PubMed, J Med Chem)
SAR studies led to the identification of compound 17, a kinase selective and highly potent CDK2 inhibitor (IC50 = 0.29 nM). The evaluation of 17 in CCNE1-amplified mouse models shows the pharmacodynamic inhibition of CDK2, measured by reduced Rb phosphorylation, and antitumor activity.
Journal
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CCNE1 (Cyclin E1)
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CCNE1 amplification
2ms
Morphologic and Molecular Heterogeneity of High-grade Serous Carcinoma Precursor Lesions. (PubMed, Am J Surg Pathol)
No correlation was observed between BLAD and Flat lesions with respect to patient age, presence of germline BRCA1/2 mutation, or p53 staining pattern. These findings suggest that tubal precursor lesions are morphologically and molecularly heterogeneous, laying the foundation for further studies on the pathogenesis of HGSC initiation and identifying histologic features predictive of poor patient outcomes.
Journal • BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CCNE1 (Cyclin E1)
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TP53 mutation • BRCA2 mutation • BRCA1 mutation • CCNE1 amplification
2ms
Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets. (PubMed, Int J Mol Sci)
Recent evidence also shows that inhibition of Cyclin-dependent kinases (CDKs), such as CDK4/6, CDK2, CDK8/19 and CDK12/13 can contribute to RS through disruption of DNA repair and replication control. Here, we review the main causes of RS in cancers as well as main therapeutic targets-ATR, CHK1, PARP and their inhibitors.
Review • Journal • PARP Biomarker
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RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1) • CDK2 (Cyclin-dependent kinase 2) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
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TP53 mutation • ATM mutation • CCNE1 amplification • RB1 mutation • TP53 amplification
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
Discovery of Tetrahydropyrazolopyrazine Derivatives as Potent and Selective MYT1 Inhibitors for the Treatment of Cancer. (PubMed, J Med Chem)
Importantly, our lead compound, featuring a tetrahydropyrazolopyrazine ring, exhibits remarkable selectivity over WEE1, a related kinase associated with bone marrow suppression upon inhibition. Optimization of potency and physical properties resulted in the discovery of compound 21, a novel MYT1 inhibitor, exhibiting optimal pharmacokinetic properties and promising in vivo antitumor efficacy.
Journal
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CCNE1 (Cyclin E1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
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CCNE1 amplification
3ms
ATR Inhibitor Elimusertib (BAY1895344) Plus Niraparib Phase 1b Study in Advanced Solid Tumors and Ovarian Cancer (clinicaltrials.gov)
P1, N=14, Terminated, Bayer | Active, not recruiting --> Terminated; There was no anticipated benefit of the experimental combination as tested over available standard therapies; therefore Sponsor has decided to terminate the investigation.
Trial termination • Combination therapy • Metastases
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CCNE1 (Cyclin E1)
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CCNE1 amplification
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Zejula (niraparib) • elimusertib (BAY 1895344)
3ms
RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov)
P2, N=78, Recruiting, Canadian Cancer Trials Group
Trial completion date • Trial primary completion date • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
|
TP53 mutation • KRAS mutation • HER-2 amplification • RAS mutation • CCNE1 amplification • UGT1A1*28 • UGT1A1*1*1
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Herceptin (trastuzumab) • gemcitabine • 5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (RP-6306)
4ms
BISCAY: Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer (clinicaltrials.gov)
P1, N=156, Active, not recruiting, AstraZeneca | Phase classification: P1b --> P1 | Trial completion date: Sep 2023 --> Jun 2024
Phase classification • Trial completion date
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HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • FGFR (Fibroblast Growth Factor Receptor) • CD8 (cluster of differentiation 8) • CCNE1 (Cyclin E1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor)
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PD-L1 expression • FGFR3 mutation • CDKN2A deletion • CCNE1 amplification • CDKN2A mutation • FGFR fusion • RB1 deletion • MYCL amplification
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Lynparza (olaparib) • Imfinzi (durvalumab) • Koselugo (selumetinib) • adavosertib (AZD1775) • fexagratinib (ABSK091) • vistusertib (AZD2014) • danvatirsen (AZD9150)
4ms
INX-315, a selective CDK2 inhibitor, induces cell cycle arrest and senescence in solid tumors. (PubMed, Cancer Discov)
Using cell-based assays, patient-derived xenografts, and transgenic mouse models, we show that INX-315 (i) promotes retinoblastoma protein hypo-phosphorylation and therapy-induced senescence (TIS) in CCNE1-amplified tumors, leading to durable control of tumor growth; (ii) overcomes breast cancer resistance to CDK4/6i, restoring cell cycle control whilst re-instating the chromatin architecture of CDK4/6i-induced TIS; and (iii) delays the onset of CDK4/6i resistance in breast cancer by driving deeper suppression of E2F targets. Our results support the clinical development of selective CDK2 inhibitors.
Journal
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CCNE1 (Cyclin E1)
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CCNE1 amplification
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INX-315
4ms
Subclonal Somatic Copy-Number Alterations Emerge and Dominate in Recurrent Osteosarcoma. (PubMed, Cancer Res)
Overall, by examining the clonal relationships between temporally and spatially separated samples from patients with relapsed/refractory osteosarcoma, this study sheds light on the intratumor heterogeneity and potential drivers of treatment resistance in this disease. The chemoresistant population in recurrent osteosarcoma is subclonal at diagnosis, emerges at the time of primary resection due to selective pressure from neoadjuvant chemotherapy, and is characterized by unique oncogenic amplifications.
Journal
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CCNE1 (Cyclin E1) • RAD21 (RAD21 Cohesin Complex Component)
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CCNE1 amplification
4ms
Testing the Combination of Two Anti-cancer Drugs, Peposertib (M3814) and M1774 for Advanced Solid Tumors (clinicaltrials.gov)
P1, N=66, Recruiting, National Cancer Institute (NCI) | Phase classification: P1b --> P1 | Initiation date: Nov 2023 --> Feb 2024
Phase classification • Trial initiation date
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ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • PBRM1 (Polybromo 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • ARID1B (AT-Rich Interaction Domain 1B) • ARID2 (AT-Rich Interaction Domain 2) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
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ATM mutation • ARID1A mutation • CCNE1 amplification • PBRM1 mutation • CCNE1 mutation
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peposertib (M3814) • tuvusertib (M1774)
5ms
Phase classification • Combination therapy • Metastases
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CCNE1 (Cyclin E1)
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CCNE1 amplification
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Zejula (niraparib) • elimusertib (BAY 1895344)
5ms
Prediction of Resistance to Lu-PSMA Therapy by Assessment of Baseline Circulating Tumor DNA Biomarkers. (PubMed, J Nucl Med)
Lu-PSMA-617 and Lu-PSMA I&T (collectively termed Lu-PSMA) are currently being used for the treatment of selected metastatic castration-resistant prostate cancer (mCRPC) patients with PSMA PET-positive disease, but biomarkers for these agents remain incompletely understood... Our analyses indicate that ctDNA assays may contain specific biomarkers predictive of response or resistance for Lu-PSMA-treated mCRPC patients. Additional confirmatory studies are required before clinicians can use these findings to make personalized treatment decisions.
Journal • Circulating tumor DNA
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FGFR1 (Fibroblast growth factor receptor 1) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12)
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FGFR1 amplification • CCNE1 amplification • CDK12 mutation
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Pluvicto (lutetium Lu 177 vipivotide tetraxetan)
5ms
Molecular characterization of endometrial carcinomas in Black and White patients reveals disparate drivers with therapeutic implications. (PubMed, Cancer Discov)
CCNE1 gene amplification, which is associated with aggressive clinical behavior, was more prevalent in carcinosarcomas occurring in Black than in White patients. ECs from Black and White patients display important differences in their histologic types, molecular subtypes, driver genetic alterations and therapeutic targets.
Journal • Tumor mutational burden • IO biomarker
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CCNE1 (Cyclin E1)
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TMB-H • CCNE1 amplification
5ms
THE ASSOCIATION OF TUMOR MOLECULAR PROFILING AND CLINICAL TRIAL ENROLLMENT IN AN ADVANCED/RECURRENT ENDOMETRIAL CANCER COHORT (IGCS 2023)
Of 1099 patients included in this study, 45 (4.1%) patients were enrolled in a trial. 31 (68.9%) of those who were enrolled in a clinical trial had undergone CGP, compared to 14 (31.1%) who had not undergone CGP (p <0.001). Those who had CGP were more likely to be enrolled in a clinical trial compared to those who did not have CGP (OR 13.55, CI 5.82 - 31.56).
Clinical • BRCA Biomarker • MSi-H 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) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability)
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HER-2 positive • TMB-H • MSI-H/dMMR • HER-2 amplification • CCNE1 amplification • BRCA2 amplification
6ms
ATR Inhibitor Elimusertib (BAY1895344) Plus Niraparib Phase 1b Study in Advanced Solid Tumors and Ovarian Cancer (clinicaltrials.gov)
P1b, N=14, Active, not recruiting, Bayer | Recruiting --> Active, not recruiting | N=89 --> 14 | Trial completion date: Mar 2025 --> Nov 2023 | Trial primary completion date: Mar 2025 --> Nov 2023
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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CCNE1 (Cyclin E1)
|
CCNE1 amplification
|
Zejula (niraparib) • elimusertib (BAY 1895344)
6ms
Testing the Combination of Two Anti-cancer Drugs, Peposertib (M3814) and M1774 for Advanced Solid Tumors (clinicaltrials.gov)
P1b, N=66, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting | Initiation date: May 2023 --> Nov 2023
Enrollment open • Trial initiation date • Combination therapy • Metastases
|
ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • PBRM1 (Polybromo 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • ARID1B (AT-Rich Interaction Domain 1B) • ARID2 (AT-Rich Interaction Domain 2) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
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ATM mutation • ARID1A mutation • CCNE1 amplification • PBRM1 mutation • CCNE1 mutation
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peposertib (M3814) • tuvusertib (M1774)
6ms
Study of ARTS-021 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
P1/2, N=192, Recruiting, Allorion Therapeutics Inc | Not yet recruiting --> Recruiting
Enrollment open • Combination therapy • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • CCNE1 (Cyclin E1)
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HER-2 negative • CCNE1 amplification
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Ibrance (palbociclib) • carboplatin • fulvestrant • letrozole • AVZO-021
6ms
Trial completion date • Metastases
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CD4 (CD4 Molecule)
|
BRCA2 mutation • BRCA1 mutation • CCNE1 amplification • BRIP1 mutation • FANCA mutation
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Lynparza (olaparib) • adavosertib (AZD1775)
7ms
P1 data
|
CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
|
CCNE1 amplification
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lunresertib (RP-6306) • camonsertib (RP-3500)
7ms
P1 data • Retrospective data • Metastases
|
CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
|
CCNE1 amplification
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lunresertib (RP-6306)
7ms
P1 data
|
CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
|
CCNE1 amplification
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lunresertib (RP-6306) • camonsertib (RP-3500)
7ms
Genomic characterization between HER2-positive and negative gastric cancer patients in a prospective trial. (PubMed, Cancer Med)
According to the genomic profiling of HER2-positive and negative gastric cancer, several gene alterations in the HER2 pathway may be the potential mechanism underlying trastuzumab resistance. Relative to HER2-positive gastric cancer, HER2-negative gastric tumors with ARID1A mutation may be sensitive to immune checkpoint inhibitors.
Journal • Tumor mutational burden • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12)
|
HER-2 positive • TP53 mutation • HER-2 amplification • HER-2 negative • PTEN deletion • ARID1A mutation • CCNE1 amplification
|
Herceptin (trastuzumab)
7ms
PKMYT1: A Potential Target for CCNE1 Amplificated Colorectal Tumors. (PubMed, Cell Biochem Biophys)
In CCNE1 amplificated colorectal tumor cells, knockdown of PKMYT1 reduced cells in S phase, inhibited cell proliferation and promoted cell apoptosis, confirming that PKMYT1 was a potential therapeutic target for colorectal tumor. This study may verify a potential therapeutic target and provide a new idea for the treatment of colorectal cancer in the future.
Journal
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CCNE1 (Cyclin E1) • CDK1 (Cyclin-dependent kinase 1) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
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CCNE1 amplification • CCNE1 overexpression • CCNE1 expression
7ms
MOLECULAR PROFILING OF P53 MUTANT ENDOMETRIAL CANCER REVEALS DISTINCT SUBGROUPS WITH OPPORTUNITIES FOR PERSONALIZED THERAPEUTIC APPROACHES (IGCS 2023)
39 P53abn cases were included in the discovery cohort. Molecular profiling was able to distinguish 4 mutually exclusive subgroups: CCNE1 amplified (15%), ERBB2 amplified (21%), PTEN alteration (21%) and a non-specific group. In the Validation Cohort, 71 P53mut EC patients were included.
HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CCNE1 (Cyclin E1)
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TP53 mutation • MSI-H/dMMR • HER-2 amplification • HER-2 mutation • CCNE1 amplification
|
FoundationOne® CDx • FoundationOne® Liquid CDx
8ms
CDK2 regulates collapsed replication fork repair in CCNE1-amplified ovarian cancer cells via homologous recombination. (PubMed, NAR Cancer)
Cyclin-dependent kinase 2, the canonical partner of cyclin E1, uniquely regulates homologous recombination in this genetic context, and as such cyclin-dependent kinase 2 inhibition synergizes with DNA damaging agents in vitro and in vivo. We demonstrate that combining a selective cyclin-dependent kinase 2 inhibitor with a DNA damaging agent could be a powerful tool in the clinic for high-grade serous ovarian cancer.
Journal
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HRD (Homologous Recombination Deficiency) • CCNE1 (Cyclin E1) • CDK2 (Cyclin-dependent kinase 2)
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HRD • CCNE1 amplification
8ms
ARTS-021-1001: Phase I/II study of ARTS-021, a potent, oral administrated, selective CDK2 inhibitor, in advanced or metastatic solid tumors (ESMO 2023)
Trial design This is a first in human, open label, multicenter phase1/2 dose escalation and dose expansion study to evaluate the safety, tolerability, PK, PD, and anti-tumor activity of ARTS-021 1) as a single agent in advanced or metastatic CCNE-1 amplifed solid tumors; 2) in combination with Carboplatin to treat refractory/resistant CCNE-1 amplified ovarian cancer that has failed standard therapies; 3) in combination with endocrine therapy (fulvestrant/letrozole) and CDK4/6 inhibitor(palbociclib/ribociclib/abemaciclib) to treat HR+ HER2- breast cancer patients have failed standard therapies. The secondary endpoint of phase 2 study will be safety/tolerability. Archival tumor and paired fresh tumor biopsy will be collected throughout the study for exploratory pharmacodynamics (PD) and biomarker evaluation.
P1/2 data • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • CCNE1 (Cyclin E1) • CDK1 (Cyclin-dependent kinase 1)
|
HER-2 negative • CCNE1 amplification
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Ibrance (palbociclib) • carboplatin • Verzenio (abemaciclib) • Kisqali (ribociclib) • fulvestrant • letrozole • AVZO-021
8ms
CCNE1 amplification defines a good prognostic subgroup among BRCAwt/HRDneg advanced high-grade ovarian cancer (HGOC) (ESMO 2023)
As expected CCNE1 amplifications are mutually exclusive from BRCA mutations, however 20% were HRD according to GIS. We observed unexpected high rates of CRS3, and significantly improved outcomes compared to non-CCNE1amp HRDneg tumors.
BRCA Biomarker • Metastases
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CCNE1 (Cyclin E1) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
HRD • CCNE1 amplification • BRCA mutation • RAD51 mutation
|
Myriad myChoice® CDx
8ms
Molecular profiling of p53 mutant endometrial cancer reveals distinct subgroups with opportunities for personalized therapeutic approaches (ESMO 2023)
Conclusions Among P53mut EC, we detected 3 nearly mutually-exclusive molecular subgroups: CCNE1 amplified, ERBB2 amplified and PTEN loss, accounting together for 60% of cases. Whether these subgroups might benefit from personalized therapeutic strategies is currently being explored.
HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CCNE1 (Cyclin E1)
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TP53 mutation • MSI-H/dMMR • HER-2 amplification • HER-2 mutation • CCNE1 amplification
|
FoundationOne® CDx • FoundationOne® Liquid CDx
8ms
Real-world results of homologous recombination deficiency testing: Comparison between two methods on 2,655 ovarian cancer patients in Spain (ESMO 2023)
Percentages of BRCAwt/GIS-, BRCAwt/GIS+, BRCAm, and invalid cases were almost identical. In conclusion, Sophia DDMTM Dx HRD solution shows a high interlaboratory agreement, providing clinically relevant molecular information, and improving the interaction between referral and reference centers.
Real-world evidence • Clinical • BRCA Biomarker • Real-world
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CCNE1 (Cyclin E1) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
|
BRCA2 mutation • BRCA1 mutation • HRD • PALB2 mutation • CCNE1 amplification • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD51 mutation
|
Myriad myChoice® CDx Plus • SOPHiA DDM HRD Solution
8ms
Homologous Recombination Deficiency Determination In Patients With High-Grade Serous Ovarian Cancer: Real-Word Experience In The French Cancer Institute Of Lorraine (ESGO 2023)
Conclusion In conclusion, we present here a 6-month activity for HRD status determination in our Institute. Our results seem consistent with the literature and the assay we use able to identify accurately patients that might benefit PARP inhibitors.
Clinical • BRCA Biomarker • PARP Biomarker
|
TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
|
TP53 mutation • BRCA1 mutation • HRD • CCNE1 amplification • HRD + BRCA1 mutation
8ms
Comprehensive Characterization Of Naïve Treatment Samples Of High Grade Serous Ovarian Cancer Addressed To Neoadjuvant Chemotherapy: A Hypothesis-Generating Study On Biomarkers Of Response To Platinum-Based Chemotherapy. (ESGO 2023)
However, MYC was associated to with a better response to NACT (28% CRS 1-2 vs 42% CRS 3).Conclusion CCNE1, MYC and PI3KCA genomic alterations seem to be associated with stages and response to chemotherapy, however, a sample size of 365 patients is required to obtain statistical significance. The enrollment is ongoing and results are expected in 2025.
Clinical
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CCNE1 (Cyclin E1)
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MYC amplification • CCNE1 amplification
|
TruSight Oncology 500 Assay
8ms
Clinical Outcomes For Presumed HRP: HGOC With CNNE1 Amplification, NF1 Loss, Or RB1 Loss (ESGO 2023)
Additionally 25% of CCNE1amp HGOC were classified as HRD on the basis of a high GIS. It is necessary to investigate the relationship between the alterations in CCNE1, NF1 or RB1 and HRD status/PARP inhibitor benefit, and validate cut-offs to define biologically relevant copy number changes for CCNE1, NF1 and RB1 in HGOC.
Clinical • Clinical data • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • CCNE1 (Cyclin E1)
|
HRD • CCNE1 amplification
9ms
Integrative analysis of a large real-world cohort of small cell lung cancer identifies distinct genetic subtypes and insights into histological transformation. (PubMed, Cancer Discov)
Finally, profiling cases of SCLC containing oncogenic drivers typically associated with NSCLC demonstrates that SCLC transformation may occur across multiple distinct molecular cohorts of NSCLC. These novel and unsuspected genetic features of SCLC may help personalize treatment approaches for this fatal form of cancer.
Journal • Real-world evidence • Real-world
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TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1)
|
TP53 mutation • STK11 mutation • CCNE1 amplification • RB1 wild-type
9ms
WEE1 inhibitor adavosertib in combination with carboplatin in advanced TP53 mutated ovarian cancer: A biomarker-enriched phase II study. (PubMed, Gynecol Oncol)
Adavosertib 225 mg BID for 2.5 days and carboplatin AUC 5 could be safely combined and showed anti-tumor efficacy in patients with PROC. However, bone marrow toxicity remains a point of concern, since this is the most common reason for dose reductions and dose delays.
P2 data • Clinical Trial,Phase II • Journal • Combination therapy • Metastases
|
TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • PROC (Protein C, Inactivator Of Coagulation Factors Va And VIIIa)
|
TP53 mutation • CCNE1 amplification
|
carboplatin • adavosertib (AZD1775)
9ms
Oncogenic structural aberration landscape in gastric cancer genomes. (PubMed, Nat Commun)
Further deconstruction of the locally clustered SVs uncovers amplicon-generating profiles characterized by super-large SVs and intensive segmental amplifications, contributing to the extensive amplification of GC oncogenes. Comprehensive analyses using adjusted SV allele frequencies indicate the significant involvement of extra-chromosomal DNA in processes linked to specific RSs.
Journal • BRCA Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • CCNE1 (Cyclin E1)
|
TP53 mutation • HER-2 amplification • CCNE1 amplification
9ms
Testing the Combination of Two Anti-cancer Drugs, Peposertib (M3814) and M1774 for Advanced Solid Tumors (clinicaltrials.gov)
P1b, N=66, Suspended, National Cancer Institute (NCI) | Not yet recruiting --> Suspended
Trial suspension • Combination therapy • Metastases
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ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • PBRM1 (Polybromo 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • ARID1B (AT-Rich Interaction Domain 1B) • ARID2 (AT-Rich Interaction Domain 2) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)
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ATM mutation • ARID1A mutation • CCNE1 amplification • PBRM1 mutation • CCNE1 mutation
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peposertib (M3814) • tuvusertib (M1774)