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    CANCER:

    Esophageal Adenocarcinoma

    Related cancers:
    1d
    AUGMENTED RESPONSE OF VOLATILE BIOMARKERS IN THE ASSESSMENT OF OESOPHAGOGASTRIC CANCER (AROMA2) (clinicaltrials.gov)
    P=N/A, N=6000, Not yet recruiting, Imperial College London
    New trial
    2d
    NCI 10211: A Phase II, Single-Arm Study of Berzosertib in Combination with Irinotecan in Patients with Advanced TP53 Mutant Gastroesophageal Cancer. (PubMed, Oncologist)
    This novel combination of ATR inhibitor berzosertib with irinotecan did not lead to objective responses in patients with TP53-mutated, advanced gastroesophageal adenocarcinoma. The combination regimen was well tolerated without unexpected adverse events. This trial was registered with ClinicalTrials.gov (NCT03641313).
    P2 data • Journal
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    TP53 (Tumor protein P53)
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    TP53 mutation
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    irinotecan • berzosertib (M6620)
    3d
    Progression-free survival as a surrogate for overall survival in gastro-esophageal cancer trials with immunotherapy: A meta-analysis. (PubMed, Eur J Cancer)
    While the correlation between treatment effects on PFS and OS was weak in ESCC, it was moderate in PD-L1-low GEA, and good in PD-L1-high GEA. Therefore, PFS is an adequate co-primary endpoint in future trials investigating novel ICIs-based regimens in GEA, especially if the analyses are pre-planned in PD-L1-high subgroups.
    Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1)
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    PD-L1 expression • PD-L1 underexpression
    4d
    NIRADO: Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (clinicaltrials.gov)
    P2, N=51, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | Trial completion date: Dec 2027 --> Feb 2025 | Suspended --> Terminated; Abandon of the partner, GSK
    Trial completion date • Trial termination • Pan tumor • Platinum sensitive
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    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • ARID2 (AT-Rich Interaction Domain 2) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)
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    HER-2 positive • HER-2 amplification • DDR • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation
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    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    4d
    Submucosal gland duct adenoma of the esophagus: expanding the morphologic spectrum of a rare tumor entity. (PubMed, Virchows Arch)
    ESGDA is a rare benign tumor arising from the esophageal duct, characterized by multiple lobulated cystic proliferation.The key diagnositic point is the presence of double layers and micropapillary/serrated structures lining the cysts. We identified BRAF V600E gene mutations in ESGDA, providing further evidence that it is the esophageal counterpart of ductal tumors and expanding the morphologic spectrum of sialadenoma papilliferum (SP)-like lesions.
    Journal
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    BRAF (B-raf proto-oncogene)
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    BRAF V600E • BRAF V600
    7d
    GRACIE: Testing Ivonescimab in Combination With Chemotherapy in Advanced or Metastatic Gastric/Gastroesophageal Adenocarcinoma (clinicaltrials.gov)
    P2, N=88, Recruiting, UNICANCER | Not yet recruiting --> Recruiting
    Enrollment open
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    paclitaxel • 5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium • Yidafan (ivonescimab)
    7d
    (VELA) Study of BLU-222 in Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=50, Terminated, Blueprint Medicines Corporation | Phase classification: P1/2 --> P1 | N=366 --> 50 | Trial completion date: Sep 2026 --> Jul 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Nov 2025 --> Jul 2025; This trial was terminated prior to the initiation of Phase 2 for reasons not due to safety concerns.
    Phase classification • Enrollment change • Trial completion date • Trial termination • Trial primary completion date
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    HER-2 (Human epidermal growth factor receptor 2) • CCNE1 (Cyclin E1)
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    HER-2 negative
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    carboplatin • Kisqali (ribociclib) • fulvestrant • cirtociclib (BLU-222)
    7d
    HPV status shapes T-cell immunoprofiles in oesophageal adenocarcinoma: high regulatory T cell infiltration predicts poor prognosis. (PubMed, J Transl Med)
    We report novel evidence of an immunoregulatory TME in HPV-negative OAC, as indicated by high Treg proportions and low CD8+:Treg ratios. Future work may lead to improved risk stratification by the presence or absence of HPV, as well as utilising the CD8+:Treg ratio in the local TME as a predictive biomarker. Additionally, a more in-depth understanding of the TME would assist in the development of novel targeted immunotherapies, for example by modulating Tregs or CD8+ T-cells.
    Journal • IO biomarker
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    CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • FOXP3 (Forkhead Box P3)
    8d
    Mutations in CREBBP and EP300 HAT and Bromo Domains Drive Hypermutation and Predict Survival in GI Cancers Treated with Immunotherapy. (PubMed, Biomedicines)
    In the gastric cancer validation cohort, all tumors with PTVs demonstrated a partial response to anti-PD-1 therapy. We report CREBBP and EP300 coding mutations as novel potential surrogate biomarkers for hypermutation in gastroesophageal adenocarcinomas and demonstrate their association with favorable immunotherapy outcomes, supporting their potential clinical utility for patient stratification.
    Journal • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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    TMB (Tumor Mutational Burden) • CREBBP (CREB binding protein) • EP300 (E1A binding protein p300)
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    TMB-H • MSI-H/dMMR
    8d
    Circulating Tumor DNA (ctDNA) in Gastroesophageal Adenocarcinoma (GEA): Evidence and Emerging Applications. (PubMed, Cancers (Basel))
    Ongoing trials are testing MRD-guided escalation/de-escalation and ctDNA-directed biomarker therapy. In this review, we evaluate the role of ctDNA in GEA cancers over recent years.
    Review • Journal • MSi-H Biomarker • Circulating tumor DNA
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    HER-2 (Human epidermal growth factor receptor 2) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2)
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    MSI-H/dMMR
    8d
    Loss of Argininosuccinate Synthetase-1 (ASS1) Occurs in Esophageal Adenocarcinoma and Represents a Promising Biomarker for Therapy with Pegargiminase. (PubMed, Cancers (Basel))
    Background/Objectives: Despite the introduction of targeted therapies such as Nivolumab, survival outcomes for patients with esophageal adenocarcinoma remain poor. This underscores the urgent need for clinical trials evaluating the efficacy of pegargiminase in this patient population. Additionally, incorporating ASS1 immunohistochemical staining into pre-neoadjuvant biopsy assessments should be considered to optimize neoadjuvant treatment strategies and advance the implementation of personalized cancer therapy.
    Journal • PD(L)-1 Biomarker
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    ASS1 (Argininosuccinate synthase 1)
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    Opdivo (nivolumab) • Hepacid (pegargiminase)
    8d
    MDM2-amplified esophageal adenocarcinomas exhibit an activated metabolic and immunosuppressive phenotype with multiple potential therapeutic targets. (PubMed, BMC Cancer)
    Summarizing, we described numerous potential therapeutic targets, suggesting patients with MDM2-amplified tumors could potentially benefit from, exemplary, Mitogen-activated protein kinase kinase inhibitors or tryptophan metabolism inhibitors in new combinational treatment regimens. Future mechanistic studies are needed to validate these findings.
    Journal
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    MDM2 (E3 ubiquitin protein ligase) • CNTN1 (Contactin 1) • HRNR (Hornerin)