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Association details:
Evidence:
Evidence Level:
Sensitive: D – Preclinical
New
Title:

The Mitogen Activated Protein Kinase Pathway Facilitates Resistance to the Src Inhibitor, Dasatinib, in Thyroid Cancer

Excerpt:
We further demonstrate that up-front combined inhibition with dasatinib and MEK1/2 or ERK1/2 inhibitors drives synergistic inhibition of growth and induction of apoptosis, indicating that combined inhibition may overcome mechanisms of survival in response to single-agent inhibition....Thus, we treated all four parental cell lines with increasing concentrations of dasatinib (0.019 – 1.25 μM) in combination with the MEK1/2 inhibitors, trametinib (0.001-0.1 μM) or selumetinib (0.05 - 0.8 μM), as well as the BCPAP and Cal62 cell lines with the ERK1/2 inhibitor, SCH772984 (0.005-0.5 μM...Additionally, combined Src and MEK1/2 inhibition also resulted in decreased clonogenic growth in both the BRAF- (BCPAP) and RAS- (Cal62) mutant cell lines in comparison to single agent treatments (Fig. S7A & B).
DOI:
10.1158/1535-7163.MCT-15-0702