ReviewFrontiers in oncology2025
The paradoxical role of stem cells in osteosarcoma: from pathogenesis to therapeutic breakthroughs.
Review in Frontiers in oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Exosomes as Cellular Communicators and Therapeutic Agents in Orthopedic Diseases: From Mechanisms to Intervention.International journal of nanomedicine · 2026Pooled it
- Stem cell transplantation in head and neck oncology: Integrating oncologic treatment and maxillofacial reconstruction.World journal of transplantation · 2026Review
- Comparative Molecular Insights and Computational Modeling of Multiple Myeloma and Osteosarcoma.International journal of molecular sciences · 2026Review
- Delayed Aggressive Local Recurrence of Chondroblastic Osteosarcoma 3 Years After an Excellent Pathological Response: A Case Report.Clinical case reports · 2026Article
- Advancements in research regarding the influence of the tumor microenvironment on the proliferation and metastasis of osteosarcoma (Review).Oncology letters · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma (OS), the most prevalent primary malignant bone tumor in adolescents, exhibits a high metastatic potential and resistance to therapy. This characteristic results in a dismal prognosis in advanced cases even following multimodal therapies. This review synthesizes the dual roles of stem cells in OS pathogenesis and therapeutic innovation. Cancer stem cells (CSCs) drive tumor initiation, progression, and chemoresistance through dysregulated molecular pathways that include Wnt/β-catenin, Notch, and Hedgehog signaling, with key markers such as CD133 and CXCR4 contributing to stemness maintenance and metastasis. Concurrently, mesenchymal stem cells (MSCs) paradoxically influence OS progression. Although their tumor-homing capacity enables targeted drug delivery (e.g., IDD-1040-paclitaxel complexes) and immunomodulation, MSC-derived factors like TGF-β can promote cancer-associated fibroblast differentiation and immune evasion. The immunosuppressive tumor microenvironment (TME), characterized by hypoxia-induced HIF-1α activation, metabolic reprogramming, and M2 macrophage polarization, further facilitates CSC resilience and therapy resistance. Emerging strategies-including CSCs-targeted agents (AZD1080, DNMTi/HDACi), CRISPR/Cas9-engineered CD133-directed CAR-T cells, and MSC-mediated delivery of oncolytic viruses-show preclinical promise in overcoming these barriers. However, critical challenges persist: intratumoral CSC heterogeneity limits targeted therapy efficacy; MSC functional plasticity risks tumor promotion via fusion or batch variations; and inefficient cell homing due to pulmonary entrapment reduces therapeutic delivery. Future directions necessitate biomarker-guided combinatorial approaches, optimized MSC administration routes (e.g., intra-arterial injection), and integrated multi-omics profiling to address translational bottlenecks. Resolving these issues will advance personalized stem cell-focused therapies for OS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.