Nucera, Nehs, Nagarkatti et al. 305 Figure 5. PLX4720 inhibits B-RafV600E-positive thyroid tumor aggressiveness in vivo. (A): Control mice with B-RafV600E 8505c orthotopic tumors (H&E stain) were large (A1) and showed extrathyroidal extension into the trachea (A1, A2) and skeletal muscle (A3) with atypical mitoses (A4, arrow); PLX4720-treated tumors (H&E stain) were small and discrete (A5–A7) (arrows) and largely confined to the thyroid bed, with atypical pyknotic nuclei (A8). (B): Control SCID mice (H&E stain) had metastatic foci of carcinoma to the lung interstitium (arrows, B1, B2) as well as a paratracheal lymph node (asterisk, (B3); higher power, arrow (B4)); PLX4720-treated mice had no evidence of metastasis to the lung (B5, B6) or lymph nodes (B7, B8). (C): PLX4720-treated tumors had greater nuclear staining for TTF-1 and PAX-8 (right) than untreated control mice (left). Abbreviations: H&E, hematoxylin and eosin; SCID, severe combined immunodeficient; TTF-1, thyroid transcription factor. DISCUSSION The typical treatment regimen of surgical excision, levo- thyroxine suppression, and radioactive iodine is successful in close to 90% of patients with differentiated thyroid can- cer. However, for the group of patients who fail to respond to this treatment paradigm or initially present with aggres- sive and refractory thyroid carcinoma, survival rates are www.TheOncologist.com very low [28]. There are very few clinical trials for thyroid cancer [29], with a partial response rate of 30% in some sin- gle-agent studies [30]. The response rate for ATC is much lower, and consequently, 50% of thyroid cancer deaths are attributed to ATC [1]. By identifying the “driving events” behind thyroid can- cer proliferation and migration/invasion, targeted molecu-