Combination of Genomic Landsscape and 3D Culture Functional Assays Bridges Sarcoma Phenotype to Target and Immunotherapy DOI Creative Commons
Filomena de Nigris,

Concetta Meo,

Wulf Palinski

и другие.

Cells, Год журнала: 2023, Номер 12(17), С. 2204 - 2204

Опубликована: Сен. 4, 2023

Genomic-based precision medicine has not only improved tumour therapy but also shown its weaknesses. Genomic profiling and mutation analysis have identified alterations that play a major role in sarcoma pathogenesis evolution. However, they been sufficient predicting vulnerability advancing treatment. The relative rarity of sarcomas the genetic heterogeneity between subtypes stand way gaining statistically significant results from clinical trials. Personalized three-dimensional models reflect specific histologic subtype are emerging as functional assays to test anticancer drugs, complementing genomic screening. Here, we provide an overview current target for discuss based on 3D that, by recapitulating molecular pathways microenvironment, may predict patient response treatments. This approach opens new avenues improve when pathway guide choice most promising Furthermore, aspects culture need be improved, such standardisation growth conditions definition vitro responses can used cut-off implementation.

Язык: Английский

Chondrosarcoma: New Molecular Insights, Challenges in Near-Patient Preclinical Modeling, and Therapeutic Approaches DOI Open Access
Lorena Landuzzi, Francesca Ruzzi, Pier‐Luigi Lollini

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1542 - 1542

Опубликована: Фев. 12, 2025

Chondrosarcoma (CS), the second most common malignant bone tumor after osteosarcoma, accounts for 20-30% of all tumors. It mainly affects adults, middle-aged, and elderly people. The CS family includes various entities displaying peculiar biological, genetic, epigenetic characteristics clinical behaviors. Conventional is subtype. High-grade, dedifferentiated, mesenchymal CS, as well unresectable metastatic exhibit poor prognoses due to their intrinsic resistance radiotherapy chemotherapy, underscoring urgent need novel therapeutic strategies. research dealing with several challenges. Experimental studies can rely on animal patient-derived models, but paucity representative near-patient preclinical models has hampered predictive drug screening research. This review describes main molecular features subtypes, discussing recent data genetic alterations mechanisms involved in pathogenesis progression. provides an overview current vitro vivo discusses advantages limitations, highlights efforts development new targeted therapies against dependencies, including IDH1/2 mutations, NAD+ dependency, SIRT1-HIF-2α axis, or exploring DR5 targeting, antiangiogenic therapies, drugs, immunological approaches. All such strategies, combination advanced modeling personalized multi-omic profiling, hold promise improving survival patients CS.

Язык: Английский

Процитировано

2

Phenotypic drug discovery DOI
Sonja Sievers, Herbert Waldmann, Slava Ziegler

и другие.

Elsevier eBooks, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0

Establishment of patient-derived 3D in vitro models of sarcomas: literature review and guidelines on behalf of the FORTRESS working group DOI
Lore De Cock, Ieva Palubeckaitė, Francesca Bersani

и другие.

Neoplasia, Год журнала: 2025, Номер 65, С. 101171 - 101171

Опубликована: Май 3, 2025

Язык: Английский

Процитировано

0

Modeling CIC::DUX4 sarcoma reveals oncogene-mediated MHCI-dependent immune evasion DOI
Ajay Ram Vachanaram,

Erdong Wei,

Ana Mitanoska

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Май 7, 2025

Abstract CIC::DUX4 sarcoma (CDS) is a highly aggressive malignancy with limited therapeutic options. Here, we present doxycycline-inducible chimeric mouse model and cancer line derived from it, imChCDS, that faithfully recapitulates the molecular, histological, immunological features of human CDS. We demonstrate expression alone sufficient to drive tumorigenesis in permissive lineages soft connective tissues. The imChCDS cell retains transcriptional footprint its mesenchymal origin, develops tumors immunocompetent hosts, exhibits clear dependency on P300/CBP co-activators. Notably, identify CIC::DUX4-mediated suppression MHC class I (MHCI) as key mechanism CDS immune evasion. Inactivation restores MHCI expression, triggers robust anti-tumor responses, leads tumor regression. Together, these models offer versatile physiologically relevant platform investigate pathogenesis, unravel evasion mechanisms, evaluate emerging strategies, including those targeting CIC::DUX4/P300/CBP oncogenic axis.

Язык: Английский

Процитировано

0

Celebrating Ulrik Ringborg: Multi-Omics-Based Patient Stratification for Precision Cancer Treatment DOI Creative Commons
Maria‐Veronica Teleanu, Annika Schneider, Claudia R. Ball

и другие.

Biomolecules, Год журнала: 2025, Номер 15(5), С. 693 - 693

Опубликована: Май 10, 2025

Precision oncology is becoming a mainstay in the standard of care for cancer patients. Recent technological advancements have significantly lowered cost various tumor profiling approaches, broadening reach molecular diagnostics and improving patient access to precision oncology. In parallel, drug development discovery pipelines continue evolve, driving targeted therapeutic options forward. Yet, not all patients harboring actionable alterations respond these interventions, existing therapies do cover entire spectrum potential targets. this review, we examine current suite omics technologies employed clinical settings underscore their roles deepening our understanding biology optimizing stratification treatments. We also highlight relevant trials share own experiences using multi-omics data within board framework. Finally, discuss areas future exploration aimed at propelling new heights.

Язык: Английский

Процитировано

0

Genomics‐led approach to drug testing in models of undifferentiated pleomorphic sarcoma DOI Creative Commons
Piotr Manasterski,

Mary K. Danks,

John P. Thomson

и другие.

Molecular Oncology, Год журнала: 2025, Номер unknown

Опубликована: Май 26, 2025

Язык: Английский

Процитировано

0

Acquired resistance in cancer: towards targeted therapeutic strategies DOI
Alice Soragni, Erik S. Knudsen, Thomas N. O’Connor

и другие.

Nature reviews. Cancer, Год журнала: 2025, Номер unknown

Опубликована: Июнь 3, 2025

Язык: Английский

Процитировано

0

Label‐Free 3D Photoacoustic Imaging of Tumor Organoids for Volumetric Drug Screening DOI Creative Commons
Xiaofei Luo,

Maike Chen,

Shan Han

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Июнь 4, 2025

Abstract As one of the most advanced in vitro drug screening platforms, tumor organoids require accurate pharmacosensitivity assessments to ensure reliable results. However, achieving volume assessment these 3D organoid models remains a challenge traditional processes. Here, label‐free photoacoustic imaging (LFOPI) system is introduced for high‐resolution organoids. The capabilities LFOPI are evaluated by monitoring structural transformations melanoma further employed volumetric Drug with cisplatin and temozolomide reveal that LFOPI‐based data correlates more strongly viability trends (0.8627 0.9069) than diameter‐based methods (0.8190 0.7849). Additionally, immunotherapy demonstrates capability precisely assess volumes irregularly shaped This provides promising method personalized treatment.

Язык: Английский

Процитировано

0

A platform for rapid patient-derived cutaneous neurofibroma organoid establishment and screening DOI Creative Commons
Huyen Thi Lam Nguyen,

Emily Kohl,

Jessica Bade

и другие.

Cell Reports Methods, Год журнала: 2024, Номер 4(5), С. 100772 - 100772

Опубликована: Май 1, 2024

Localized cutaneous neurofibromas (cNFs) are benign tumors that arise in the dermis of patients affected by neurofibromatosis type 1 syndrome. cNFs lesions: they do not undergo malignant transformation or metastasize. Nevertheless, can cover a significant proportion body, with some individuals developing hundreds to thousands lesions. cause pain, itching, and disfigurement resulting substantial socio-emotional repercussions. Currently, surgery laser desiccation sole treatment options but may result scarring potential regrowth from incomplete removal. To identify effective systemic therapies, we introduce an approach establish screen cNF organoids. We optimized conditions support ex vivo growth genomically diverse cNFs. Patient-derived organoids closely recapitulate cellular molecular features parental as measured immunohistopathology, methylation, RNA sequencing, flow cytometry. Our organoid platform enables rapid screening compounds patient- tumor-specific manner.

Язык: Английский

Процитировано

2

Let’s get functional: Drug sensitivity profiling to enable precision sarcoma medicine DOI
Claudia R. Ball, Stefan Fröhling

Cell stem cell, Год журнала: 2024, Номер 31(10), С. 1389 - 1390

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

1