AI Article Synopsis
- The study designed to investigate the effectiveness of anlotinib, a drug used for osteosarcoma, and its combination with chemotherapy in patient-derived xenograft (PDX) models.
- Researchers created 21 successful PDX models from osteosarcoma specimens, using six of them for experiments with anlotinib and a placebo, revealing that anlotinib inhibited tumor growth significantly.
- The findings indicated that osteosarcoma tumors with high levels of VEGFR2 and PDGFRβ were more responsive to anlotinib treatment, showing tumor regression in four out of five patients treated prior to surgery, although further research on the drug's combined effectiveness with chemotherapy is required.
Article Abstract
Background: The aim of this study was to analyze the potential therapeutic targets of anlotinib using the patient-derived xenografts (PDX) and evaluate the efficacy of the combination of chemotherapy and anlotinib in osteosarcoma patients before surgery.
Methods: Forty-three osteosarcoma specimens were used to establish the PDX model in mice, resulting in Twenty-one PDX successful models. Eventually, six models were randomly selected for the pharmacodynamic experiment. The tumor-bearing mice were randomly divided into the anlotinib (3 mg/kg) and placebo groups (n = 5 each). After treatment, the tumors were harvested and analyzed by immunohistochemistry (IHC) and western blotting.
Results: In PDX model establishment, the tumors from donors with relapse, metastasis or chemoresistance demonstrated higher engraftment capacity. Histology results suggested that anlotinib significantly inhibited the growth of osteosarcoma by inducing mitotic arrest, necrosis and apoptosis, and selective against tumors with high expression of VEGFR2, PDGFRβ and CD31. Based on these results, five osteosarcoma patients who had progressed during NAC were treated with the combination of anlotinib and chemotherapy before surgery, which led to tumor regression in four patients. Next-generation sequencing showed that most patients with tumor reduction expressed medium or high levels of VEGFR2 and PDGFRβ mRNA. The toxicities were tolerable.
Conclusions: In conclusion, osteosarcoma with high expression of VEGFR2, PDGFRβ and CD31 is more sensitive to anlotinib. However, the potential of synergistic effect of anlotinib and chemotherapy in osteosarcoma patients needs further investigation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609326 | PMC |
| http://dx.doi.org/10.1002/cam4.70416 | DOI Listing |
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