Chondrosarcoma: New Molecular Insights, Challenges in Near-Patient Preclinical Modeling, and Therapeutic Approaches

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1542 - 1542

Published: Feb. 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.

Language: Английский

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Targeting PI3K Signaling to Overcome Tumor Immunosuppression: Synergistic Strategies to Enhance Cancer Vaccine Efficacy

Vaccines, Journal Year: 2025, Volume and Issue: 13(3), P. 292 - 292

Published: March 10, 2025

Phosphoinositide 3-kinases (PI3Ks), members of the lipid kinase family, play a significant role in modulating immune cell functions, including activation, proliferation, and differentiation. Recent studies have identified PI3K signaling pathway as key regulator tumor biology microenvironment. This enhances activity regulatory T cells (Tregs) myeloid-derived suppressor (MDSCs), contributing to an immunosuppressive microenvironment that impairs effectiveness cancer vaccines immunotherapies. The present study explores isoforms, particularly p110γ p110δ, their associated pathways. therapeutic potential selective inhibitors capacity act synergistically with immunization strategies are analyzed. Targeting represents promising approach counteract tumor-induced suppression improve efficacy checkpoint vaccines, ultimately leading better clinical outcomes.

Language: Английский

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Topology‐Oriented Lymph Node Drainage of Dendritic Polymer‐TLR Agonist Conjugates to Enhance Vaccine Immunogenicity

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Strategically targeting lymph nodes (LNs) to orchestrate the initiation and regulation of adaptive immune responses is one most pressing challenges in context vaccination. Herein, a series polymer-TLR agonist conjugates (PTACs) developed investigate impact dendritic-topological characteristics on their LN activity vivo, molecular weight (MW) pharmacokinetics support homing. Notably, dendritic 6-arm PTAC with MW 60 kDa (6A-PTAC-60k) rapidly delivered cargo draining LNs after administration peripheral tissues. Specifically, this topologic structure ameliorated behavior within lymphatic vessels LNs, including an elevated amount TLR7/8 improved distribution pattern among barrier cells cells, increased permeability, prolonged retention. Furthermore, 6A-PTAC-60k formulation induced broad antibody T cell responses, enhancing vaccine immunogenicity suppressing tumor growth. The results revealed that both topology polymers are crucial factors for immunoadjuvant functional which, turn, enhanced formulation. This study may provide chemical structural basis optimizing design delivery systems.

Language: Английский

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Exosome‐Based Vaccines: Pioneering New Frontiers in Combating Infectious Diseases and Cancer

Small Methods, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Abstract Exosomes, small extracellular vesicles with lipid bilayer membranes, play a crucial role in cellular communication and can transfer diverse biological cargo, including proteins, lipids, nucleic acids, from donor to recipient cells. Exosomes possess immunological properties, such as antigen delivery immune activation, along excellent drug capabilities, making them promising candidates for vaccine development. For different diseases, exosome‐based vaccines be designed therapeutic or prophylactic by leveraging immunity humoral immunity. With the emergence of precision medicine, personalized demonstrate exceptional potential. This review systematically introduces sources, biogenesis mechanisms, components exosomes describes their regulatory roles system. Subsequently, preparation, administration, therapy are discussed. Finally, applications clinical trials fields anti‐infection anti‐tumor therapies particularly highlighted, an analysis potential challenges future

Language: Английский

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