306 PLX4720 and Preclinical Thyroid Cancer Models Figure 6. Gene expression with PLX4720 treatment. Quantitative real-time RT-PCR shows mRNA copy number of CCND1 (A), TSP-1 (B), ITGA6 (C), and TTF-1 (D) mRNA in 8505c and TPC-1 cells after 24 hours or 72 hours of treatment with PLX4720 (either 1 M or 10 M). Abbreviations: CCND1, cyclin D1; ITGA6, integrin 6; RT-PCR, reverse transcriptase polymerase chain reaction; TSP-1, thrombospondin-1; TTF-1, thyroid transcription factor; wt, wild-type. lar agents hold great potential for aggressive thyroid cancer. Current molecular strategies involve interrupting intracel- lular signal transduction pathways at specific targets, such as B-Raf, Ras, MEK, PI3K, RET, cMet, and epidermal growth factor [31]. Given that B-RafV600E is the most prev- alent mutation implicated in the initiation and aggressive- ness of PTC, and possibly in the progression of PTC to ATC [31, 32], targeting this mutation holds great potential for