Osteosarcoma, the most common bone malignancy in children and adolescents, poses considerable challenges in terms of prognosis, especially for patients with metastatic or recurrent disease. While surgical intervention and adjuvant chemotherapy have improved survival rates, limitations such as impractical tumor removal or chemotherapy resistance hinder the treatment outcomes. Chimeric antigen receptor (CAR)-T cell therapy, an innovative immunotherapy approach that involves targeting tumor antigens and releasing immune factors, has shown significant advancements in the treatment of hematological malignancies. However, its application in solid tumors, including osteosarcoma, is constrained by factors such as low antigen specificity, limited persistence, and the complex tumor microenvironment. Research on osteosarcoma is ongoing, and some targets have shown promising results in pre-clinical studies. This review summarizes the current status of research on CAR-T cell therapy for osteosarcoma by compiling recent literature. It also proposes future research directions to enhance the treatment of osteosarcoma.

Background: The proto‐oncogene ROS1 encodes an intrinsic type I membrane protein of the tyrosine kinase/insulin receptor family. ROS1 facilitates the progression of various malignancies via self‐mutations or rearrangements. Studies on ROS1‐directed tyrosine kinase inhibitors have been conducted, and some have been approved by the FDA for clinical use. However, the adverse effects and mechanisms of resistance associated with ROS1 inhibitors remain unknown. In addition, next‐generation ROS1 inhibitors, which have the advantage of treating central nervous system metastases and alleviating endogenous drug resistance, are still in the clinical trial stage.Method: In this study, we searched relevant articles reporting the mechanism and clinical application of ROS1 in recent years; systematically reviewed the biological mechanisms, diagnostic methods, and research progress on ROS1 inhibitors; and provided perspectives for the future of ROS1‐targeted therapy.Results: ROS1 is most expressed in malignant tumours. Only a few ROS1 kinase inhibitors are currently approved for use in NSCLC, the efficacy of other TKIs for NSCLC and other malignancies has not been ascertained. There is no effective standard treatment for adverse events or resistance to ROS1‐targeted therapy. Next‐generation TKIs appear capable of overcoming resistance and delaying central nervous system metastasis, but with a greater incidence of adverse effects.Conclusions: Further research on next‐generation TKIs regarding the localization of ROS1 and its fusion partners, binding sites for targeted drugs, and coadministration with other drugs is required. The correlation between TKIs and chemotherapy or immunotherapy in clinical practice requires further study.

Objective: Osteosarcoma is a rare primary malignant tumor of the bone characterized by poor survival rates, owing to its unclear pathogenesis. Rho GTPase-activating protein 44 (ARHGAP44), which belongs to the Rho GTPase-activating protein family, has promising applications in the targeted therapy of tumors. Therefore, this study aimed to investigate the biological function of ARHGAP44 in osteosarcoma and its possible application as a therapeutic target. Methods: The expression level of ARHGAP44 in osteosarcoma and its relationship with tumor prognosis were detected using Gene Expression Omnibus database analysis and immunohistochemical staining of clinical specimens. The cell model of ARHGAP44 knockdown was constructed, and the effects of this gene on the malignant biological behavior of osteosarcoma cells were investigated using CCK-8, clone formation, transwell invasion, wound healing, and flow cytometry assays. Western blotting was performed to detect the expression of ARHGAP44, p53, C-myc, and Cyclin D1 in osteosarcoma. Results: Biogenic analysis showed that ARHGAP44 was highly expressed in osteosarcoma. This result was associated with poor tumor prognosis and negatively correlated with the expression of the tumor suppressor gene p53. Immunohistochemistry and western blotting revealed significantly upregulated expression of ARHGAP44 in osteosarcoma tissues. Additionally, Kaplan–Meier analysis of clinical specimens suggested that ARHGAP44 was negatively correlated with tumor prognosis. CCK-8, clone formation, transwell invasion, wound healing, and flow cytometry assays showed that downregulation of ARHGAP44 expression significantly reduced the malignant biological behavior of osteosarcoma cells. Furthermore, western blotting showed that the expression level of p53 in osteosarcoma cells was significantly increased after the downregulation of ARHGAP44 expression, whereas the expression of C-myc and Cyclin D1 was significantly decreased compared with that in the control group. Conclusion: ARHGAP44 was highly expressed in osteosarcoma and was negatively correlated with its prognosis. The downregulation of ARHGAP44 expression reduced the malignant biological behavior of osteosarcoma cells. These findings suggest that the downregulation of ARHGAP44 expression inhibits the malignant progression of osteosarcoma by regulating the p53/C-myc/Cyclin D1 pathway, demonstrating the potential of ARHGAP44 as a therapeutic target for osteosarcoma.