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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Cabozantinib as an emerging treatment for sarcoma
Patrick Schöffski1, Jean-Yves Blay2, Isabelle Ray-Coquard3
1Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
Purpose Of Review:
Sarcomas are a diverse group of rare solid tumors with limited treatment options for patients with advanced, inoperable disease. Cabozantinib is a tyrosine kinase inhibitor currently approved for advanced renal cell, hepatocellular, and medullary thyroid carcinoma. Cabozantinib has potent activity against a variety of kinases, including MET, vascular endothelial growth factor receptor, and AXL, that are associated with sarcoma growth and development. Here we review the preclinical findings and clinical development of cabozantinib in the treatment of soft tissue sarcoma, gastrointestinal stromal tumors (GIST), osteosarcoma, and Ewing sarcoma.
Recent Findings:
In vitro, cabozantinib has shown relevant activity in inhibiting the growth and viability of soft tissue sarcoma, GIST, osteosarcoma, and Ewing sarcoma tumor cell lines. Cabozantinib also promoted the regression of GIST in various murine xenografts, including imatinib-resistant models. More than 10 prospective trials with cabozantinib that included patients with sarcomas have been completed or are currently ongoing. Clinical activity with cabozantinib has been recently reported in phase 2 clinical trials for patients with GIST and for patients with osteosarcoma or Ewing sarcoma.
Summary:
Cabozantinib has shown promising activity for the treatment of various sarcomas, supporting further evaluation in this setting.
Insights
Cabozantinib shows promise for treating rare sarcomas, including soft tissue sarcoma, GIST, osteosarcoma, and Ewing sarcoma. Further clinical evaluation is supported by preclinical and early clinical trial findings.
Area of Science:
- Oncology
- Pharmacology
Background:
- Sarcomas are rare solid tumors with limited treatment options for advanced disease.
- Cabozantinib targets kinases like MET, VEGF, and AXL, crucial in sarcoma development.
Purpose of the Study:
- To review preclinical and clinical data of cabozantinib in treating various sarcoma types.
- To assess cabozantinib's efficacy in soft tissue sarcoma, GIST, osteosarcoma, and Ewing sarcoma.
Main Methods:
- Review of preclinical studies demonstrating cabozantinib's in vitro and in vivo anti-sarcoma activity.
- Analysis of ongoing and completed prospective clinical trials involving cabozantinib for sarcoma patients.
Main Results:
- Cabozantinib inhibited growth and viability in multiple sarcoma cell lines in vitro.
- Tumor regression observed in GIST murine xenografts, including imatinib-resistant models.
- Phase 2 trials reported clinical activity in GIST, osteosarcoma, and Ewing sarcoma.
Conclusions:
- Cabozantinib exhibits promising activity against diverse sarcoma types.
- Further investigation of cabozantinib for sarcoma treatment is warranted.
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