Redifferentiation of a BRAF^K601E-Mutated Poorly Differentiated Thyroid Cancer Patient with Dabrafenib and Trametinib Treatment

The molecular and gene/miRNA expression profiles of radioiodine resistant papillary thyroid cancer

“…In this context it was demonstrated that in mouse thyroid cancers with conditional BRAF V600E expression the lack of radioiodine incorporation depend on BRAF activity [57]. In the clinical setting, promising data on redifferentiation have been obtained with new compounds targeting BRAF or MEK, such as Vemurafenib, Dabrafenib, Trametinib, and Selumetinib, though the anti-tumor effect is variable, ranging from a partial to a null response, possibly due to the histopathological and genetic heterogeneity of mutated tumors [11][12][13][14][15][16][17][18][19]. Finally, based on the original data obtained in the present work, future studies will be particularly focused on the possible effects of RET/PTC oncogenes on RAI uptake, since to the best of our knowledge no data are available on this topic.…”

“…Based on these in vitro and in vivo data, pilot studies and phase 2 trials demonstrated that two selective BRAF inhibitors, namely Vemurafenib and Dabrafenib, are able to stimulate radioiodine uptake in patients with metastatic BRAF V600E -mutant RAI-R DTCs [11][12][13][14][15][16]. In addition, attempts of reverse RAI refractoriness in TC patients restoring radioiodine uptake, have been conducted with MEK inhibitors, tested as single agent [17] or, more recently, in combination with BRAF inhibitors [18,19].…”

A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the European Thyroid Association, the Society of Nuclear Medicine and Molecular Imaging on Current Diagnostic and Theranostic Approaches in the Management of Thyroid Cancer

“…The theranostic power of RAI imaging, compromised by aberrant MAPK output along with other pathways and epigenetic events, may be improved with MAPK modulators, similar to TSH stimulation. Currently the clinical data are limited but very compelling, backed by physiological considerations (34)(35)(36)(37)(38).…”

A spotlight on redifferentiation strategies and target modulation in differentiated thyroid cancer

“…Other clinical trials are ongoing (EudraCT No 2015-002, 269-47, NCT03244956 NCT04554680, NCT04619316) and preliminary data seem to support better results in terms of objective response using the combination of different drugs targeting MEK and BRAF to induce a more robust MAPK pathway inhibition [8].…”