Biology subjects

Meryet-Figuiere, M.

Publications and source records attributed to Meryet-Figuiere, M..

3 recordsLinked to original sources

bioRxiv2026

Predicting Head and Neck Squamous Cell Carcinoma outcomes using long-term Patient-Derived Tumor Organoids

Head and neck squamous cell carcinoma (HNSCC) remains associated with substantial morbidity and a 5-year overall survival rate of approximately 60%, reflecting persistent radio- and chemo-resistance and the lack of effective precision medicine strategies. Patient-Derived Tumor Organoids (PDTO) constitute promising functional models that may predict individual treatment response. In this study, we generated PDTO from surgically resected HNSCC of the oral cavity, oropharynx, larynx, and hypopharynx. A total of 20 long-term PDTO lines were established, maintaining growth over seven passages and successfully cryopreserved, capturing the molecular and clinical diversity of the patient cohort. These PDTO faithfully recapitulated histological features, major tumor marker expression, and the genomic and transcriptomic landscapes of their tumors of origin, with stability over time. Functional assays revealed heterogeneous responses to cisplatin and X-rays. Importantly, in vitro sensitivity of PDTO was associated with clinical outcome of patients at 24 months. Cisplatin response of PDTO predicted prognosis with 66.7% sensitivity and 100% specificity, while X-ray response showed 91.7% sensitivity and 75% specificity. Notably, all patients whose PDTO were classified as resistant to both cisplatin and X-rays experienced relapse and/or death within 24 months. Collectively, the successful long-term expansion and cryopreservation of HNSCC PDTO establish a stable and scalable preclinical resource that captures the molecular and clinical heterogeneity of the disease. This biobank provides a valuable platform for mechanistic studies and for the evaluation of innovative therapeutic strategies. This cohort represents one of the largest clinically annotated HNSCC PDTO collections to date, demonstrating a robust association between PDTO response to cisplatin and X-rays and patient prognosis. These findings support the predictive potential of PDTO-based functional assays and argue for their integration into standardized, rapid, and miniaturized precision oncology workflows for HNSCC.

cancer biology↗

bioRxiv2025

Integrative in silico and experimental identification of non-covalent UBE2N inhibitors enhancing PARP inhibitor sensitivity

UBE2N, an E2 ubiquitin-conjugating enzyme, has emerged as a compelling therapeutic target in oncology due to its critical roles in DNA damage repair and NF-{kappa}B signalling. While covalent inhibitors have shown preclinical promise, non-covalent inhibitors offer potential advantages in terms of selectivity and reduced off-target effects. However, structural and mechanistic data for non-covalent UBE2N inhibitors remain scarce. To address this gap, we implemented a dual in silico strategy combining structure-based molecular docking and ligand-based 3D pharmacophore modelling. Screening a home library of [~]19,000 compounds targeting both the ubiquitin-binding and cofactor interfaces of UBE2N, we identified 22 candidates suitable for biological evaluation. Among these, two compounds, CERMN-2 and CERMN-16, emerged as promising non-covalent inhibitors. CERMN-16, structurally related to the natural compound Variabine B (identified through 3D pharmacophore screening), significantly reduced SKOV-3 ovarian cancer cell viability and enhanced their sensitivity to the PARP inhibitor Olaparib. CERMN-2, identified through docking, also demonstrated a synergistic effect with Olaparib and showed low toxicity in normal ovarian epithelial cells. Molecular dynamics simulations indicated distinct binding modes for each compound, consistent with their targeted binding sites. Biophysical experiments revealed weak binding of CERMN-16 to UBE2N, whereas CERMN-2 bound UBE2N in two orthogonal assays (Microscale thermophoresis and Nano differential scanning fluorimetry). CERMN-16, and more importantly CERMN-2, therefore represent promising leads for the development of selective, non-natural, non-covalent UBE2N inhibitors. These results provide new insights into UBE2N inhibition and support further investigation of their mechanisms of action and therapeutic potential in combination cancer therapies. HIGHLIGHTSO_LIDual in silico screening (docking and 3D pharmacophore) identified new non-covalent UBE2N inhibitor candidates. C_LIO_LITwo compounds, CERMN-2 and CERMN-16, displayed synergistic activity with Olaparib in ovarian cancer cells. C_LIO_LIMD simulations revealed distinct, site-specific binding modes for both compounds. C_LIO_LIBiophysical assays confirmed UBE2N binding for CERMN-2, identifying it as a promising non-natural, non-covalent lead. C_LI

cancer biology↗

bioRxiv2025

Long-term patient-derived ovarian cancer organoids closely recapitulate tumor of origin and clinical response

There is an urgent need of precision medicine for ovarian cancer patients to identify patients who respond to chemotherapy and PARP inhibitors, a therapy targeting homologous recombination deficiency (HRD). Here we established a panel of 37 long-term patient-derived tumor organoids (PDTO) models of various histological subtypes from 224 patients and demonstrated that they mimic the histological and molecular characteristics of original tumors. Screening of chemotherapeutic drugs showed that PDTO exhibit heterogeneous responses, and that response of PDTO from high-grade serous ovarian carcinoma to carboplatin recapitulated patient response to first-line treatment. Additionally, the detection of HRD phenotype of PDTO using functional assay was associated with the results of the HRD test Genomic Instability Scar (GIScar). Although larger-scale investigations are needed to confirm the predictive potential of PDTO, these results provide further evidence of the potential interest of ovarian PDTO for functional precision medicine even if many challenges remain to be addressed.

cancer biology↗