^
    over1year
    Establishment and characterization of multiple patient-derived organoids from a case of advanced endometrial cancer. (PubMed, Hum Cell)
    Lastly, a drug screening identified four candidate reagents commonly effective to all PDOs. Collectively, we showed that multiple PDOs could help reproduce the spatial diversity of a tumor and serve as a valuable resource in UCS research in many respects.
    Journal • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • CCNE1 (Cyclin E1)
    |
    TP53 mutation • KRAS mutation • HER-2 amplification • HER-2 mutation • HER-2 expression • STK11 mutation • CCNE1 amplification • CCNE1 mutation
    almost2years
    The genomic and immune landscapes of gastric cancer and their correlations with HER2 amplification and PD-L1 expression. (PubMed, Cancer Med)
    The combination of HER2 amplification and PD-L1 expression in Chinese patients with GC could stratify the total populations into several subgroups with distinctive genomic and immune landscapes, which should be considered when making personalized treatment decisions.
    Journal • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • KMT2D (Lysine Methyltransferase 2D) • CDH1 (Cadherin 1)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • HER-2 expression • ARID1A mutation • MYC amplification • PD-L1 amplification • HER-2 amplification + PD-L1 expression • CCNE1 mutation
    2years
    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
    |
    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)
    |
    ATM mutation • ARID1A mutation • CCNE1 amplification • PBRM1 mutation • CCNE1 mutation
    |
    peposertib (M3814) • tuvusertib (M1774)
    2years
    Cell Cycle Regulators Across Solid Tumors (AMP 2023)
    Across solid tumors, alterations associated with sensitivity to CDK4/6 inhibitors varied widely in frequency. Though the frequency of alterations in CDK4/6 inhibitor resistance genes was generally low, identifying such patients may be critical for decisions regarding the use of CDK4/6 inhibitors.
    Tumor mutational burden
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • 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) • CCNE1 (Cyclin E1) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FGF3 (Fibroblast growth factor 3)
    |
    TMB-H • HER-2 negative • CCNE1 mutation
    |
    OncoExTra™ test
    2years
    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)
    |
    ATM mutation • ARID1A mutation • CCNE1 amplification • PBRM1 mutation • CCNE1 mutation
    |
    peposertib (M3814) • tuvusertib (M1774)
    over2years
    Homologous recombination deficiency (HRD) testing on ovarian cancer ascites: A feasibility study (ESMO 2023)
    Conclusions This exploratory study showed that HRD testing on cytological specimens from EOC ascites is feasible but standardized pre-analytical procedures are required to ensure adequate samples for the analysis. Ascites might represent a valid alternative for early BRCA1/2 and HRD status evaluation in women with EOC when tissue samples are inadequate/insufficient.
    BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CCNE1 (Cyclin E1) • BRCA (Breast cancer early onset)
    |
    TP53 mutation • HRD • BRCA wild-type • CCNE1 mutation
    |
    SOPHiA DDM HRD Solution
    over2years
    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
    |
    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)
    |
    ATM mutation • ARID1A mutation • CCNE1 amplification • PBRM1 mutation • CCNE1 mutation
    |
    peposertib (M3814) • tuvusertib (M1774)
    over2years
    Mesonephric-like Adenocarcinoma of the Female Genital Tract: Novel Observations and Detailed Molecular Characterisation of Mixed Tumours and Mesonephric-like Carcinosarcomas. (PubMed, Histopathology)
    Our observations provide additional evidence that MLAs have a Müllerian origin and characterise mesonephric-like carcinosarcomas in which chondroid elements appear to be characteristic. In reporting these findings, we provide recommendations for distinction between a mesonephric-like carcinosarcoma and a MLA with a spindle cell component.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog) • CCNE1 (Cyclin E1) • CREBBP (CREB binding protein)
    |
    KRAS mutation • EGFR mutation • PTEN mutation • CCNE1 mutation
    over2years
    Clinical implications of tumor-based next-generation sequencing in high-grade epithelial ovarian cancer. (PubMed, Cancer)
    Although more and more patients with ovarian cancer are undergoing tumor-based next-generation sequencing to identify genetic mutations in their tumors, the benefits of such testing are not well established. In a group of over 400 patients with ovarian cancer who underwent tumor-based next-generation sequencing in the course of their treatment, nearly all patients had one or more genetic alterations detected, and one out of four patients had a mutation that qualified them for a personalized treatment option.
    Retrospective data • Journal • Next-generation sequencing • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • NF1 (Neurofibromin 1) • CCNE1 (Cyclin E1) • AKT2 (V-akt murine thymoma viral oncogene homolog 2)
    |
    TP53 mutation • BRCA2 mutation • BRCA1 mutation • PIK3CA mutation • NF1 mutation • CCNE1 amplification • BRCA1 mutation + BRCA2 mutation • AKT2 amplification • CCNE1 mutation
    over2years
    CCNE1 amplification in high-grade serous ovarian cancer: analysis of the GENIE database (AACR 2023)
    Somatic sequencing is warranted to identify patients of this subset of HGSOC, and understanding the co-amplifications and co-mutations is essential so that they are targeted for optimal survival outcomes.
    BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • CCNE1 (Cyclin E1) • KMT2D (Lysine Methyltransferase 2D) • CDK12 (Cyclin dependent kinase 12) • TSC2 (TSC complex subunit 2) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • BRD4 (Bromodomain Containing 4)
    |
    TP53 mutation • KRAS mutation • PIK3CA mutation • PTEN mutation • CCNE1 amplification • KMT2D mutation • TSC2 mutation • CCNE1 mutation
    over2years
    Establishment and characterization of a panel of breast XPDX models representing innate or acquired resistance to trastuzumab deruxtecan (T-DXd) (AACR 2023)
    These models, designated ST4565C, ST4565D, STM148B, STM148C, STM148D, and ST4480B/EHR were developed and characterized for receptor expression, genomics, and drug sensitivities toward chemotherapies and targeted agents including T-DXd, T-DM1, and margetuximab. ST4565C/D was established from a patient with ER+/HER2+, metastatic BC who was T-DXd treatment naïve. ST4565C was collected post chemo- and HER2-targeted therapies; ST4565D was collected following eribulin/margetuximab... We established and characterized six breast XPDX models representing innate or acquired resistance to T-DXd. These models are valuable tools in understanding resistance mechanisms and in developing novel therapies for T-DXd-resistant patients.
    Preclinical
    |
    ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NOTCH3 (Notch Receptor 3) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • CCDC170(Coiled-Coil Domain Containing 170)
    |
    PIK3CA mutation • PIK3CA E545K • CDKN2A deletion • FGFR1 fusion • FGFR1 expression • CCND1 expression • PIK3CA E545 • ER-CCDC170 fusion • CCNE1 mutation
    |
    Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Halaven (eribulin mesylate) • Margenza (margetuximab-cmkb)
    almost3years
    Testing the Combination of Two Anti-cancer Drugs, Peposertib (M3814) and M1774 for Advanced Solid Tumors (clinicaltrials.gov)
    P1b, N=66, Not yet recruiting, National Cancer Institute (NCI)
    New P1 trial • 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)
    |
    ATM mutation • ARID1A mutation • CCNE1 amplification • PBRM1 mutation • CCNE1 mutation
    |
    peposertib (M3814) • tuvusertib (M1774)