A Phase I Trial of the VEGF Receptor Tyrosine Kinase Inhibitor Pazopanib in Combination with the MEK Inhibitor Trametinib in Advanced Solid Tumors and Differentiated Thyroid Cancers.
As a result of BRAF kinase inhibition, reduction in MEK kinase activity was seen (p < 0.05) in both thyroid cancer cell lines (72 and 75 %, respectively).
The objective of this study was to use a potent new-generation MEK inhibitor PD0325901 to further investigate the therapeutic potential of specifically targeting MEK in the MAP kinase pathway for thyroid cancer.
Moreover, a phenotypic reversion is also observed with a partial restoration of normal thyroid marker transcription, and thyroid cancer marker expression reduction.In conclusion, combination therapy of MEK and Pi3'-kinase inhibition synergizes to target double mutant thyroid cancer in vitro and in vivo.
Thus, these results demonstrated the important therapeutic potential of the novel MEK inhibitor RDEA119 and its synergism with temsirolimus in thyroid cancer.