Advancements in Osteosarcoma Therapy: Overcoming Chemotherapy Resistance and Exploring Novel Pharmacological Strategies

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 520 - 520

Published: April 3, 2025

Osteosarcoma is recognized as the most prevalent primary bone malignancy, primarily affecting children and adolescents. It characterized by its aggressive behavior high metastatic potential, which often leads to poor patient outcomes. Despite advancements in surgical techniques chemotherapy regimens, prognosis for patients with osteosarcoma remains unsatisfactory, survival rates plateauing over past few decades. A significant barrier effective treatment development of resistance, complicates management disease contributes recurrence. This review article aims provide a comprehensive overview recent therapy, particularly overcoming resistance. We begin discussing current standard modalities, including resection conventional agents such methotrexate, doxorubicin, cisplatin. While these approaches have been foundational managing osteosarcoma, they are limited adverse effects variability efficacy among patients. To address challenges, we explore novel pharmacological strategies that aim enhance includes targeted therapies focusing on specific molecular alterations cells immunotherapeutic designed harness body’s immune system against tumors. Additionally, innovative drug delivery systems improve bioavailability existing treatments while minimizing toxicity. The also assesses mechanisms underlying efflux mechanisms, altered metabolism, enhanced DNA repair pathways. By synthesizing research findings, highlight potential new therapeutic resistance mechanisms. Ultimately, this seeks inform future directions clinical practices, underscoring need continued innovation treating outcomes rates.

Language: Английский

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Histopathology of Non-odontogenic Neoplasms of the Jaws

Published: Jan. 1, 2025

Language: Английский

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Decoding the function of Cancer-Associated Fibroblasts in Osteosarcoma: Molecular pathways, therapeutic approaches and prognostic significance

Experimental Cell Research, Journal Year: 2025, Volume and Issue: unknown, P. 114612 - 114612

Published: May 1, 2025

Language: Английский

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Exploratory Analysis of Molecular Subtypes in Early-Stage Osteosarcoma: Identifying Resistance and Optimizing Therapy

Cancers, Journal Year: 2025, Volume and Issue: 17(10), P. 1677 - 1677

Published: May 16, 2025

Background: Osteosarcoma (OS) is a highly aggressive bone malignancy with limited treatment options and poor prognosis. This exploratory study aimed to identify molecular subtypes of early-stage, treatment-naive OS guide precise therapeutic strategies. Methods: We analyzed RNA-seq data obtained from tumor tissues 102 patients using non-negative matrix factorization algorithm (NMF) classify the tumors into three subtypes: S1, S2, S3. Differential gene expression was evaluated DESeq2, followed by functional enrichment analysis clusterProfiler CancerHallmarks. The microenvironment assessed through ESTIMATE CIBERSORT, drug sensitivity predicted OncoPredict. SAOS-2 MG63 cells, representing S1 subtype, were used in viability essays determine effect hesperidin, natural phenolic compound noted for its anti-cancer potential, alone combination doxorubicin 5-fluorouracil. Results: revealed enriched cell cycle regulation, vesicular transport, RNA metabolism while S2 S3 pathways related extracellular organization protein translation, respectively. displayed high purity, significant chemoresistance, overexpression KIF20 A, correlating AURKB, hesperidin target, implicated pathogenesis. In vitro, significantly reduced cells enhanced efficacy. Conclusions: Our findings support subclassification OS, emphasizing subtype-specific mechanisms progression offering potential as adjunct high-risk patients.

Language: Английский

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The landscape of drug sensitivity and resistance in sarcoma

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

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Targeting the EphA2 pathway: could it be the way for bone sarcomas?

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 9, 2024

Language: Английский

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Enhanced Biomimetics of Three-Dimensional Osteosarcoma Models: A Scoping Review

Cancers, Journal Year: 2023, Volume and Issue: 16(1), P. 164 - 164

Published: Dec. 28, 2023

This scoping review evaluated 3D osteosarcoma (OS) models’ biomimicry, examining their ability to mimic the tumour microenvironment (TME) and drug sensitivity. Adhering PRISMA-ScR guidelines, systematic search revealed 293 studies, with 70 selected for final analysis. Overall, 64% of OS models were scaffold-based, compared self-generated spheroid models. Scaffolds generated using native matrix most common (42%) collagen I/hydroxyapatite predominating. Both scaffold-based scaffold-free used equally screening. The sensitivity cancer cells in was reported be lower than that 2D ~90% screening studies. correlates observed upregulation resistance. cultured extracellular (ECM)-mimetic scaffolds biomaterials more resistant 2D. Co-cultures stromal enhanced osteogenic differentiation, ECM remodelling, mineralisation, angiogenesis, suggesting tumour–stroma crosstalk promotes disease progression. Seven studies demonstrated selective toxicity chemotherapeutics towards while sparing cells, providing useful evidence developing biomimetic test toxicity. In conclusion, this highlights need enhance biomimicry TME recapitulation, especially testing novel therapeutics. Future research should explore innovative models, biomaterials, advancements personalised medicine.

Language: Английский

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FGF23 Expression Is a Promising Immunohistochemical Diagnostic Marker for Undifferentiated Pleomorphic Sarcoma of Bone (UPSb)

Genes, Journal Year: 2024, Volume and Issue: 15(2), P. 242 - 242

Published: Feb. 14, 2024

Background: Undifferentiated pleomorphic sarcoma of bone (UPSb) is a rare primary that lacks specific line differentiation. Distinguishing between UPSb and other malignant sarcomas, including dedifferentiated chondrosarcoma osteosarcoma, challenging due to their overlapping features. We have previously identified tumours elevated mRNA levels Fibroblast Growth Factor 23 (FGF23) transcripts compared sarcomas osteosarcoma. In the present study, we evaluated specificity practicality FGF23 immunoreactivity as diagnostic tool differentiate from osteosarcomas chondrosarcomas. Methods: A total 10 UPSb, cases (all high-grade), were retrieved immunohistochemistry for was performed. Results: protein expressed at high in 80–90% undifferentiated cases, whereas it significantly lower osteosarcoma cases. semiquantitative analysis, considering intensity immunoreactivity, confirmed expression tissues those observed tissues. Conclusions: The results here suggest may be useful aid differentiating morphologically similar especially situations where sampling restricted there limited clinical information available.

Language: Английский

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Comprehensive single cell transcriptomics analysis of murine osteosarcoma uncovers Skp2 function in metastasis, genomic instability and immune activation and reveals additional target pathways

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 6, 2024

ABSTRACT Osteosarcoma (OS) is the most common primary pediatric bone malignancy. One promising new therapeutic target SKP2 , encoding a substrate recognition factor of SCF E3 ubiquitin ligase responsible for ubiquitination and proteasome degradation p27, thus driving cellular proliferation. We have shown previously that knockout Skp2 in an immunocompetent transgenic mouse model OS improved survival, drove apoptosis, induced tumor inflammation. Here, we applied single-cell RNA-sequencing (scRNA-seq) to study tumors derived from Osx-Cre driven conditional Rb1 Trp53 . showed murine models recapitulate heterogeneity microenvironment complexity observed patient tumors. further compared this with functional disruption : one other Skp2-p27 interaction disrupted (resulting p27 overexpression). found reduction T cell exhaustion upregulation interferon activation, along evidence replicative endoplasmic reticulum-related stress models, induction was correlated survival patients. Additionally, our scRNA-seq analysis uncovered decreased activities metastasis-related gene signatures -disrupted OS, which validated by observation strong lung metastasis mice. Finally, report several potential mechanisms escape targeting including Myc targets, DNA copy number amplification overexpression alternative genes, lineage activation. These mechanistic insights into biology function suggest novel targets new, synergistic therapies, while data comprehensive may serve as public resource big data-driven research.

Language: Английский

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Successful remission of a recurrent metacarpal osteosarcoma of a Warmblood gelding after radiation therapy

Equine Veterinary Education, Journal Year: 2024, Volume and Issue: 37(2)

Published: Oct. 1, 2024

Summary A 15‐year‐old Warmblood gelding was presented with recurrence of a histologically confirmed osteosarcoma the left second and third metacarpal bones 3 years after initial diagnosis treatment. Initially, surgical excision performed, followed by local injection carboplatin 11 weeks later. The horse sound surgery used for low‐level dressage jumping. Three later, developed an acute onset lameness in forelimb painful soft tissue swelling at proximomedial region. Radiographs showed spiculated periosteal reaction on medial aspect bone, indicating re‐activation lesion. Stereotactic radiation therapy performed protocol consisting three fractions under general anaesthesia (Mo‐We‐Fr schedule), total dose 30 Gy. technique volumetric‐modulated arc guided cone beam computed tomography daily positioning. Following therapy, became walk, 1 month it trot. Follow‐up veterinary examination 18 months final treatment revealed no walk trot, stable radiographic appearance.

Language: Английский

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