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Updated: Jun 6, 2025
Author Spotlight: Replicating Human Osteosarcoma Progression in Immunodeficient Mice for Cancer Study
Published on: March 22, 2024
The Potential Therapeutic Targets of Anlotinib in Osteosarcoma: Characterization Based on Patient-Derived Xenografts
Zuoyao Long1,2, Yajie Lu2, Minghui Li2
1General Hospital of Northern Theater Command, Shenyang, China.
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.
Insights
Anlotinib effectively targets osteosarcoma by inhibiting growth and inducing cell death, particularly in tumors expressing high levels of VEGFR2, PDGFRβ, and CD31. Combination therapy showed promising results in patients, warranting further investigation.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Osteosarcoma remains a challenging malignancy with limited treatment options.
- Identifying novel therapeutic targets and effective combination strategies is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate anlotinib's therapeutic targets in osteosarcoma using patient-derived xenografts (PDX).
- To evaluate the efficacy of combining chemotherapy with anlotinib in osteosarcoma patients prior to surgery.
Main Methods:
- Establishment of 21 osteosarcoma PDX models from 43 specimens.
- Pharmacodynamic experiments in mice using anlotinib (3 mg/kg) vs. placebo.
- Immunohistochemistry (IHC) and western blotting for molecular analysis.
- Next-generation sequencing (NGS) for mRNA expression analysis.
Main Results:
- Anlotinib demonstrated significant osteosarcoma growth inhibition via mitotic arrest, necrosis, and apoptosis.
- Sensitivity to anlotinib was associated with high expression of VEGFR2, PDGFRβ, and CD31.
- Four out of five osteosarcoma patients treated with anlotinib and chemotherapy showed tumor regression.
- Tolerable toxicity profiles were observed in clinical application.
Conclusions:
- Osteosarcoma with high VEGFR2, PDGFRβ, and CD31 expression is sensitive to anlotinib.
- The combination of anlotinib and chemotherapy shows potential synergistic effects in osteosarcoma.
- Further clinical investigation is warranted to confirm the synergistic potential.
