Cabozantinib is a chemotherapeutic compound that has shown potential as a treatment for medullary thyroid cancer and other types of solid tumors. It is primarily known for its inhibition of c-Met and vascular endothelial growth factor receptor 2 (VEGFR-2). By inhibiting these tyrosine kinases Cabozantinib reduces tumor growth, metastasis, and angiogenesis.
In a 2016 study, cabozantinib showed activity against gastrointestinal stromal tumors (GIST). In many cases of GIST, oncogenic signaling is driven by KIT mutations. Tyrosine kinase inhibitors (TKI) such as imatinib have been used to treat GIST, but resistance to TKI caused by secondary mutations to KIT sometimes renders this treatment ineffective.
Cabozantinib was tested in patient-derived xenograft models of GIST, with each model carrying different KIT mutations. Three different models were examined in total, and in all three cabozantinib inhibited proliferative activity, even in those models that were imatinib-resistant. Compared to an imatinib treated group and a control group, cabozantinib also significantly reduced microvessel density in all three models.
From the study it was concluded that cabozantinib shows promising antitumor activity in both imatinib-sensitive and imatinib-resistant GIST models. The activity is achieved through the inhibition of tumor growth, proliferation, and angiogenesis, and may provide a valid alternate treatment method for GIST going forward.
Gebreyohannes Y., Schoffski P., et al. Cabozantinib is Active against Human Gastrointestinal Stromal Tumor Xenografts Carrying Different KIT Mutations. Mol Cancer Ther; 15(12); 2845-52.