Early Study of Lestaurtinib in Anaplastic Thyroid Cancer
Posted: Wednesday, December 19, 2018
A new study published in PLOS One provides in vitro and in vivo evidence that the JAK2 inhibitor lestaurtinib is an antiproliferative agent with potential antiangiogenic activity. Anthony C. Nichols, MD, of Western University, London, Ontario, Canada, and his colleagues reported data suggesting that lestaurtinib should be further investigated as a targeted therapy in patients with anaplastic thyroid cancer.
Researchers utilized 13 different anaplastic thyroid cancer cell lines to test lestaurtinib in vitro. Nanomolar concentrations of the drug were able to reduce proliferation in 11 of the 13 cell lines, and it impeded both cell migration and colony formation. Flow-cytometry analysis revealed that although apoptosis was not initiated, arrest at the G2/M phase of the cell cycle did occur with treatment. In addition, knockout of JAK2 in anaplastic thyroid cancer cell lines treated with lestaurtinib suggested that the drug’s antiproliferative effects may be due to more than just JAK2 inhibition, as the knockout cell lines still showed decreased proliferation after drug treatment.
Further analysis in vivo was completed using chick chorioallantoic membrane xenograft models. Tissue treated with lestaurtinib had an endpoint mean tumor volume of 1.7 mm3, whereas the mean tumor volume of untreated tissue was 4.05 mm3. This decrease in endpoint tumor volume was accompanied by a decrease in vascularity.
“Overall, the data in this study suggest that lestaurtinib is an effective and valid therapeutic agent in the study of [anaplastic thyroid cancer]; however, this drug warrants further investigation to understand the full potential as a targeted therapy in [anaplastic thyroid cancer],” the authors concluded.