Proteoglycan Research, Journal Year: 2024, Volume and Issue: 2(4)
Published: Oct. 1, 2024
Abstract Sarcomas are a heterogeneous group of aggressive mesenchymal malignancies. They account for 1% all tumors in the general population and 15–20% pediatric age young adults. Despite differences histology pathobiology, diverse types sarcomas traditionally managed with common multi‐modal approach including surgery, radiotherapy, polychemotherapy. Unfortunately, prognosis advanced or recurrent disease remains poor. Moreover, rarity high cellular, molecular, genetic/epigenetic heterogeneity make identification therapeutic targets challenging. Therefore it an urgent need to identify effective therapies improve patients' outcome. Common peculiar biological motifs deregulation growth factor signaling, proangiogenic promigratory pathways, tumor‐microenviroment interactions, transcriptional epigenetic machinery, differentiation program, provide actionable dependencies exploitable intervention. Among these, deregulated heparan sulfate proteoglycan system due aberrant expression key components as well structural/functional modifications mediated by endosulfatases endoβ‐ d ‐glycosidase heparanase, is emerging crucial player tumor progression valuable target across different sarcoma subtypes. In preclinical studies, non‐anticoagulant heparins have been shown counteract metastatic dissemination various models according their mimetic anti‐heparanase activities. Heparin derivatives also improved anti‐sarcoma efficacy molecularly targeted agents cytotoxic drugs. this minireview, we summarize current knowledge about interplay between heparanase/heparan pathways involved sarcomagenesis progression. We illustrate understanding mechanisms action contribution anti‐heparanase, anti‐receptor tyrosine kinase, likely immunomodulatory activities effects. Finally, discuss few aspects worthy exploration highlighting how elucidation underpinning antitumor heparin contexts may suggest new vulnerabilities approaches.
Language: Английский