The Landscape of Immunotherapy for Retroperitoneal Sarcoma DOI Creative Commons
Alicia A. Gingrich, Elise F. Nassif, Christina L. Roland

et al.

Current Oncology, Journal Year: 2023, Volume and Issue: 30(2), P. 2144 - 2158

Published: Feb. 9, 2023

Significant multidisciplinary scientific effort has been undertaken to understand the heterogeneous family of neoplasms that comprise soft tissue sarcomas. Within this neoplasms, outcomes for retroperitoneal sarcomas (RPS) are currently limited given a lack effective therapies. In review, we focus on immunotherapy and its relationship with common RPS histologic subtypes. Although initial patients immune checkpoint inhibition alone have somewhat disappointing, subsequent analyses histologies, tumor microenvironment, sarcoma class, infiltrating lymphocytes genetic analysis mutational burden yielded insight into interplay between immunotherapy. Such approaches all provided critical environment characterization these tumors, targets potential in future clinical trials. With insight, molecularly tailored combination treatments improving response rates oncologic promising.

Language: Английский

The landscape of drug sensitivity and resistance in sarcoma DOI Creative Commons
Ahmad Al Shihabi, Peyton Tebon, Huyen Thi Lam Nguyen

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

7
Untargeted Metabolomics and Liquid Biopsy Investigation of Circulating Biomarkers in Soft Tissue Sarcoma DOI Open Access
Daniela Grasso, Barbara Marzocchi, Guido Scoccianti

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 553 - 553

Published: Feb. 6, 2025

Background: Soft tissue sarcomas (STSs) are rare, highly malignant mesenchymal tumours, comprising approximately 1% of all adult cancers and about 15% paediatric solid tumours. STSs exhibit considerable genomic complexity with diverse subtypes, posing significant clinical challenges. Objectives: This study aims to characterise the molecular signature primary STS through liquid biopsies untargeted metabolomic profiling 75 patients, providing deep insights into cellular processes potential therapeutic targets. Methods: analysed serum samples using nuclear magnetic resonance (NMR) spectroscopy for profiling. Multivariate data analysis machine learning classifiers were employed identify biomarkers. Results: A panel eleven deregulated metabolites discovered in patients STS, implications cancer diagnosis treatment. Conclusions: Choline decrease emerged as a marker progression, highlighting targeting its metabolism approaches STS. The NMR protocol proved effective determining circulating biomarkers from biopsies, making it suitable rare disease research.

Language: Английский

Citations

0
A Review on Canine and Human Soft Tissue Sarcomas: New Insights on Prognosis Factors and Treatment Measures DOI Creative Commons
Filippo Dell’Anno, Roberta Giugliano, Valeria Listorti

et al.

Veterinary Sciences, Journal Year: 2024, Volume and Issue: 11(8), P. 362 - 362

Published: Aug. 10, 2024

Soft tissue sarcomas (STSs) represent a diverse group of tumors arising from mesenchymal cells, affecting both humans and animals, including dogs. Although STSs class rare tumors, especially in humans, they pose significant clinical challenges due to their potential for local recurrence distant metastasis. Dogs, as model human STSs, offer several advantages, exposure similar environmental risk factors, genetic diversity among breeds, the spontaneous development tumors. Furthermore, canine closely mimic heterogeneity complexity making them valuable research into disease progression treatment effectiveness. Current approaches dogs primarily involve surgery, radiation therapy, chemotherapy, with decisions based on tumor characteristics patient factors. However, novel therapeutic strategies is essential, given high failure rate new drugs trials. To better design tailored treatments, comprehension microenvironment (TME) fundamental, since it plays crucial role STS initiation by modulating behavior, promoting angiogenesis, suppressing immune responses. Notably, TME features include cancer-associated fibroblasts (CAFs), extracellular matrix (ECM) alterations, tumor-associated macrophages (TAMs) that, depending polarization state, can affect responses thus patient's prognosis. In this review, therapeutical immunotherapy will be deeply explored options STSs. conclusion, review provides an overview current understanding emphasizing importance strategies.

Language: Английский

Citations

3
HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study DOI Creative Commons
David S. Moura, José L. Mondaza-Hernández,

Paloma Sánchez-Bustos

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: May 17, 2024

Abstract HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of for trabectedin in advanced soft-tissue sarcoma (STS) effect inhibiting or mTOR downstream pathway activity. The expression was assessed cohort 301 STS patients at mRNA (n = 133) protein level 272), by HTG EdgeSeq transcriptomics immunohistochemistry, respectively. silencing on activity gene profiling measured leiomyosarcoma cells. combining inhibitors cell viability vitro studies, whereas vivo studies tested this combination. were significantly worse progression-free survival overall STS. sensitized cells treatment, reducing spheroid area increasing death. downregulation HGMA1 decreased enrichment some specific sets, including PI3K/AKT/mTOR pathway. inhibition mTOR, cultures In combination rapamycin downregulated stabilized growth 3-methylcholantrene-induced sarcoma-like models. an adverse prognostic treatment increases efficacy, part modulating signaling Trabectedin plus are active preclinical models sarcoma, downregulating levels stabilizing growth.

Language: Английский

Citations

3
Metabolic landscapes in sarcomas DOI Creative Commons
Richard MIALLOT, Franck Galland,

Virginie Millet

et al.

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: July 22, 2021

Abstract Metabolic rewiring offers novel therapeutic opportunities in cancer. Until recently, there was scant information regarding soft tissue sarcomas, due to their heterogeneous origin, histological definition and underlying genetic history. Novel large-scale genomic metabolomics approaches are now helping stratify physiopathology. In this review, we show how various alterations skew activation pathways orient metabolic sarcomas. We provide an update on the contribution of newly described mechanisms regulation. underscore that relevant sarcomagenesis or shared with other cancers. then discuss diverse landscapes condition tumor microenvironment, anti-sarcoma immune responses prognosis. Finally, review current attempts control sarcoma growth using metabolite-targeting drugs.

Language: Английский

Citations

16
A Detailed Examination of Retroperitoneal Undifferentiated Pleomorphic Sarcoma: A Case Report and Review of the Existing Literature DOI Open Access

Goran Balovic,

Bojana Stojanović,

Dragče Radovanović

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(13), P. 3684 - 3684

Published: June 25, 2024

This detailed review focuses on retroperitoneal undifferentiated pleomorphic sarcoma (UPS), a particularly aggressive soft-tissue that poses unique diagnostic and therapeutic challenges due to its rarity complex presentation. By documenting new case of UPS conducting comprehensive all known cases, this article aims expand the existing body knowledge epidemiology, molecular pathogenesis, treatment strategies associated with rare disease. The complexity diagnosing is emphasized given it rarely occurs in space histological often complicates recognition. highlights need for specialized approaches, including advanced imaging techniques histopathological studies, accurately diagnose stage In terms treatment, paper advocates multidisciplinary approach combines surgery, radiotherapy chemotherapy tailors individual patients optimize outcomes. studies illustrate effectiveness surgical intervention these tumors emphasize importance achieving clear margins prevent recurrence. Furthermore, discusses potential targets innovative therapies could bring hope affected by challenging sarcoma.

Language: Английский

Citations

2
Dysregulation of miRNAs in Soft Tissue Sarcomas DOI Creative Commons
Stefano Zoroddu, Angela Lucariello, Antonio De Luca

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1853 - 1853

Published: Nov. 8, 2024

MicroRNAs (miRNAs) are pivotal regulators of gene expression, influencing key cellular processes such as proliferation, differentiation, apoptosis, and metastasis. In the realm sarcomas-a diverse group malignant tumors affecting soft tissues bone sarcomas-miRNAs have emerged crucial players in tumorigenesis tumor progression. This review delves into intricate roles miRNAs across various tissue sarcoma subtypes, including rhabdomyosarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, fibrosarcoma, angiosarcoma, undifferentiated pleomorphic (UPS), peripheral nerve sheath (MPNST). We explore how dysregulated function oncogenes or suppressors, modulating critical pathways that define aggressive nature these cancers. Furthermore, we discuss diagnostic prognostic potential specific highlight their promise therapeutic targets. By understanding miRNA-mediated regulatory networks, this aims to provide a comprehensive overview current research while pointing towards future directions for miRNA-based therapies. Our findings underscore transform landscape treatment, offering hope more precise, personalized, effective strategies.

Language: Английский

Citations

2
Inflammatory leiomyosarcoma/rhabdomyoblastic tumor: A report of two cases with novel genetic findings DOI
Madina Sukhanova, Farres Obeidin, Lukas D. Streich

et al.

Genes Chromosomes and Cancer, Journal Year: 2022, Volume and Issue: 61(11), P. 653 - 661

Published: June 3, 2022

Inflammatory leiomyosarcoma (ILMS) is a malignant neoplasm showing smooth muscle differentiation, prominent inflammatory infiltrate, and near-haploidization. These tumors have significant pathologic genetic overlap with the recently described "inflammatory rhabdomyoblastic tumor (IRT)," suggesting that ILMS IRT may belong to one entity. Herein, we describe two cases of ILMS/IRT attention new cytogenetic sequencing findings. The were composed sheets fascicles variably pleomorphic cells spindled epithelioid rhabdoid morphology histiocyte-rich infiltrate typical ILMS/IRT. In case 1, chromosomal microarray analysis showed near-haploid pattern loss heterozygosity resulting from copy all autosomes except for chromosomes 5, 20, 21, 22. Case 2 areas high-grade rhabdomyosarcomatous transformation. this case, low-grade component revealed hyper-diploid most but normal diploid number state 22, which relative gain. similar copy-neutral additional abnormalities, including mosaic segmental gains at 1p, 5p, 8q, 9p, 20q, 8p. Next-generation identified sequence variants in NF1, TP53, SMARCA4, KRAS, MSH6. MSH6 variant was confirmed as germline, consistent diagnosis hereditary nonpolyposis colorectal cancer (HNPCC) syndrome our study patients suggestive might be part HNPCC spectrum.

Language: Английский

Citations

11
The landscape of drug sensitivity and resistance in sarcoma DOI Open Access
Ahmad Al Shihabi, Peyton Tebon, Huyen Thi Lam Nguyen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 26, 2023

Abstract Sarcomas are a family of rare malignancies composed over 100 distinct histological subtypes. The rarity sarcoma poses significant challenges in conducting clinical trials to identify effective therapies, the point that many rarer subtypes do not have standard-of-care treatment. Even for established regimens, there can be substantial heterogeneity responses. Overall, novel, personalized approaches identifying treatments needed improve patient out-comes. Patient-derived tumor organoids (PDTOs) clinically relevant models representative physiological behavior tumors across an array malignancies. Here, we use PDTOs as tool better understand biology individual and characterize landscape drug resistance sensitivity sarcoma. We collected n=194 specimens from n=126 patients, spanning 24 characterized 120 biopsy, resection, metastasectomy samples. leveraged our organoid high-throughput screening pipeline test efficacy chemotherapeutics, targeted agents, combination with results available within week tissue collection. Sarcoma showed patient-specific growth characteristics subtype-specific histopathology. Organoid correlated diagnostic subtype, age at diagnosis, lesion type, prior treatment history, disease trajectory subset compounds screened. found 90 biological pathways were implicated response bone soft organoids. By comparing functional responses genetic features tumors, show how PDTO provide orthogonal set information facilitate optimal selection, avoid ineffective mirror outcomes In aggregate, able least one FDA-approved or NCCN-recommended regimen 59% tested, providing estimate proportion immediately actionable identified through pipeline. Highlights Standardized culture preserve unique histopathological Drug on patient-derived provides correlates yields guidance High-throughput screenings sequencing therapy Large scale, precision medicine programs cancers feasible single institution

Language: Английский

Citations

6
Chip-Based and Wearable Tools for Isothermal Amplification and Electrochemical Analysis of Nucleic Acids DOI Creative Commons

Claudia Patiti,

Patrick Severin Sfragano, Serena Laschi

et al.

Chemosensors, Journal Year: 2022, Volume and Issue: 10(7), P. 278 - 278

Published: July 14, 2022

The determination of nucleic acids has become an analytical diagnostic method with many applications in fields such as biomedical sciences, environmental monitoring, forensic identification, and food safety. Among the different methods for acid analysis, those based on polymerase chain reaction (PCR) are nowadays considered gold standards. Isothermal amplification interesting alternative, especially design chip-based architectures. Biosensing platforms hold great promise simple rapid detection since they can be embedded lab-on-a-chip tools to perform extraction, amplification, steps. Electrochemical transduction schemes particularly small portable devices due miniaturization, low-energy consumption, multianalyte capability. aim this review is summarize isothermal combined electrochemical biosensing techniques development wearable sensors. Different revised, examples discussed. Finally, a discussion patented also included.

Language: Английский

Citations

7