Background
B-RafV600E is a frequent mutation in anaplastic thyroid cancers and is a novel therapeutic target.
We hypothesized that PLX4720 (an inhibitor of B-RafV600E) and thyroidectomy would extend survival and would decrease tumor burden in a mouse
model.
Methods
Orthotopic anaplastic thyroid tumors were induced in severe combined immunodeficient
mice. Mice were treated with PLX4720 or vehicle after 7 days of tumor growth, and
thyroidectomy or sham surgery was performed at day 14. The neck space was re-explored,
and tumor volume was measured at day 35. Mice were sacrificed when they lost >25%
of their initial weight.
Results
All 5 mice that received the vehicle developed cachexia, had invasive tumors (average
61 mm3)and were sacrificed by day 35. All 6 mice receiving PLX4720 + sham had small tumors
(average 1.3 mm3) and maintained their weight. Three out of 6 mice receiving PLX4720+thyroidectomy
had no evidence of tumor at 35 days; the other 3 mice had small tumors (average 1.4
mm3) and showed no signs of metastatic disease. All mice treated with PLX4720 were alive
and well-appearing at 50 days.
Conclusion
Thyroidectomy with neoadjuvant PLX4720 could be an effective therapeutic strategy
for early anaplastic thyroid cancers that harbor the B-RafV600E mutation and are refractory to conventional therapeutic modalities.
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Article info
Publication history
Accepted:
September 13,
2010
Footnotes
Supported by the NIH T32 Grant #5T32 DK007754-10.
Identification
Copyright
© 2010 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
