Treatment Effect of Combining Lenvatinib and Vemurafenib for BRAF Mutated Anaplastic Thyroid Cancer
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Background and Objectives: Even though most of the thyroid cancer shows good prognosis, de-differentiatedthyroid cancer is still refractory to conventional treatments. Recently, kinase inhibitors including multi-kinase andBRAF inhibitors are widely used for treatment of de-differentiated thyroid cancers, but resistant to single kinaseinhibitor treatment eventually encountered. Therefore, combination therapy may have better therapeutic effectthan single therapy for thyroid cancer. In this study, we evaluated therapeutic effect of multi-kinase and BRAFinhibitor combination to anaplastic thyroid cancer cell lines with and without BRAF mutation. Materials andMethods: We used anaplastic thyroid cancer cell lines with BRAFV600E mutation (8505C) and with NRAS mutation(HTh7). Both cell lines were treated with various concentration of multi-kinase inhibitor (lenvatinib) and BRAFinhibitor (vemurafenib). And combination of various concentration of both kinase inhibitors were used to treatboth cell lines. Cytotoxic effect was assessed with cell counting kit-8 and therapeutic effect of single kinaseinhibitor therapy and the combination therapy was compared. Results: Anti-proliferative effect of vemurafenibon 8505C BRAFV600E-mutated cells was demonstrated from 0.25 μM concentration. However, HTh7 cells withNRAS mutation represented drug resistance up to 4 μM of vemurafenib. In case of lenvatinib treatment as amulti-kinase inhibitor, 8505C and HTh7 cells showed decreased cell viability dose-dependent manner. Combinationtreatment with vemurafenib and lenvatinib showed synergistic cytotoxic effect in BRAF mutated 8505C cell line,even at lower concentrations. Conclusion: Combination treatment with multi-kinase inhibitor and BRAF inhibitorshowed promising therapeutic results in BRAF mutated anaplastic thyroid cancer cell line.
Abstract
Background and Objectives: Even though most of the thyroid cancer shows good prognosis, de-differentiatedthyroid cancer is still refractory to conventional treatments. Recently, kinase inhibitors including multi-kinase andBRAF inhibitors are widely used for treatment of de-differentiated thyroid cancers, but resistant to single kinaseinhibitor treatment eventually encountered. Therefore, combination therapy may have better therapeutic effectthan single therapy for thyroid cancer. In this study, we evaluated therapeutic effect of multi-kinase and BRAFinhibitor combination to anaplastic thyroid cancer cell lines with and without BRAF mutation. Materials andMethods: We used anaplastic thyroid cancer cell lines with BRAFV600E mutation (8505C) and with NRAS mutation(HTh7). Both cell lines were treated with various concentration of multi-kinase inhibitor (lenvatinib) and BRAFinhibitor (vemurafenib). And combination of various concentration of both kinase inhibitors were used to treatboth cell lines. Cytotoxic effect was assessed with cell counting kit-8 and therapeutic effect of single kinaseinhibitor therapy and the combination therapy was compared. Results: Anti-proliferative effect of vemurafenibon 8505C BRAFV600E-mutated cells was demonstrated from 0.25 μM concentration. However, HTh7 cells withNRAS mutation represented drug resistance up to 4 μM of vemurafenib. In case of lenvatinib treatment as amulti-kinase inhibitor, 8505C and HTh7 cells showed decreased cell viability dose-dependent manner. Combinationtreatment with vemurafenib and lenvatinib showed synergistic cytotoxic effect in BRAF mutated 8505C cell line,even at lower concentrations. Conclusion: Combination treatment with multi-kinase inhibitor and BRAF inhibitorshowed promising therapeutic results in BRAF mutated anaplastic thyroid cancer cell line.
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