Thursday, June 26, 2014
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Studies in patient samples
and cell culture suggest BRAF and SMO inhibitors could be useful for treating
ameloblastomas, which are rare, typically benign tumors that form in the jaw.
Whole-transcriptome sequencing of ameloblastoma samples from 28 patients
showed that 11 had SMO mutations and 13 had BRAF mutations, all
of which were primarily activating mutations. In an immortalized mouse ameloblast-lineage
cell line that expressed one of the identified activating mutations in Smo,
pathway inhibitor Trisenox
trioxide decreased hedgehog pathway activity compared with
vehicle. In a human ameloblastoma cell line that expressed one of the
identified activating mutations in BRAF, the BRAF inhibitor Zelboraf
blocked proliferation with an IC50 value of 0.19 mM.
Next steps could include developing animal models of ameloblastoma and using
them to evaluate drugs that inhibit the hedgehog pathway or BRAF.
Pharmaceutical Industries Ltd., H.
Lundbeck A/S and Nippon
Shinyaku Co. Ltd. market Trisenox to treat acute
promyelocytic leukemia (APL).
Sankyo Co. Ltd. and Chugai
Pharmaceutical Co. Ltd. market Zelboraf to treat melanoma.
Published online June 26, 2014
Patent and licensing status
Sweeney, R.T. et al.
Nat. Genet.; published online May 25, 2014;
Contact: Robert B. West, Stanford University Medical Center,
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