The management of osteosarcoma (OS) patients presents a significant clinical challenge. Despite progress in conventional and targeted therapies, the survival rate of OS patients remains limited largely due to therapy resistance and the high metastatic potential of the disease. OS models that accurately reflect the fundamental characteristics are vital to the innovation and validation of effective therapies. This review provides an insight into the advances and challenges in OS drug development, focusing on various preclinical models, including cell lines, 3D culture models, murine models, and canine models. The relevance, strengths, and limitations of each model in OS research are explored. In particular, we highlight a range of potential therapeutics identified through these models. These instances of successful drug development represent promising pathways for personalized OS treatment.

Osteosarcoma, a predominant malignant bone tumor, poses significant challenges due to its high metastatic and recurrent nature. Although various therapeutic strategies are currently in use, they often inadequately target osteosarcoma metastasis. This review focuses on the potential of nanoscale drug delivery systems to bridge this clinical gap. It begins with an overview of the molecular mechanisms underlying metastatic osteosarcoma, highlighting the limitations of existing treatments. The review then transitions to an in-depth examination of nanoscale drug delivery technologies, emphasizing their potential to enhance drug bioavailability and reduce systemic toxicity. Central to this review is a discussion of recent advancements in utilizing nanotechnology for the potential intervention of metastatic osteosarcoma, with a critical analysis of several preclinical studies. This review aims to provide insights into the potential applications of nanotechnology in metastatic osteosarcoma therapy, setting the stage for future clinical breakthroughs and innovative cancer treatments.

Sarcoma is a heterogeneous group of mesenchymal neoplasms with a high rate of lung metastasis. The cellular mechanisms responsible for sarcoma metastasis remain poorly understood. Furthermore, there are limited efficacious therapeutic strategies for treating metastatic sarcoma. Improved diagnostic and therapeutic modalities are of increasing importance for the treatment of sarcoma due to their high mortality in the advanced stages of the disease. Recent evidence demonstrates that the exosome, a type of extracellular vesicle released by virtually all cells in the body, is an important facilitator of intercellular communication between the cells and the surrounding environment. The exosome is gaining significant attention among the medical research community, but there is little knowledge about how the exosome affects sarcoma metastasis. In this review, we summarize the multifaceted roles of sarcoma-derived exosomes in promoting the process of metastasis via the formation of pre-metastatic niche (PMN), the regulation of immunity, angiogenesis, vascular permeability, and the migration of sarcoma cells. We also highlight the potential of exosomes as innovative diagnostic and prognostic biomarkers as well as therapeutic targets in sarcoma metastasis.

Introduction: Gastric cancer (GC) exhibits a poor prognosis with high metastasis rates. This study investigates Vitamin D receptor’s (VDRs) role in suppressing GC metastasis through autophagy. Objective: To elucidate the molecular mechanism by which VDR suppresses GC invasion and metastasis through autophagy regulation. Methods: VDR expression was assessed in 91 paired GC and adjacent normal tissues using immunohistochemistry. The effects of Vitamin D on GC cell proliferation, cell cycle, migration, and invasion were evaluated using Cell Counting Kit-8, flow cytometry, wound healing, and Transwell assays. The autophagic activity was examined through LysoTracker Red staining, monomeric red fluorescent protein-green fluorescent protein-LC3 fluorescence, and transmission electron microscopy. The roles of VDR, autophagy-related protein 13 (ATG13), and Beclin1 in autophagy regulation were investigated through gene knockdown and silencing. A nude mouse peritoneal metastasis model was used to validate the anti-metastatic effects of the Vitamin D/VDR pathway. Results: VDR expression was significantly downregulated in GC tissues, correlating with lymph node metastasis and poor prognosis (p<0.001). Vitamin D treatment upregulated VDR, ATG13, and Beclin1 expression, enhancing autophagosome and autolysosome formation without altering cell proliferation or apoptosis, likely due to a cytostatic autophagic response. Silencing ATG13 or BECN1 abolished the inhibitory effects of Vitamin D/VDR signaling on cell migration and invasion. VDR knockdown promoted peritoneal metastasis, whereas Vitamin D treatment suppressed it. Conclusion: This study provides novel evidence that Vitamin D/VDR signaling inhibits GC metastasis by influencing ATG13/Beclin1-mediated autophagy, offering potential therapeutic targets for GC management.