Journal
THYROID
Volume 32, Issue 5, Pages 594-598Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/thy.2021.0524
Keywords
differentiated thyroid cancer; radioactive iodine resistance; NTRK; larotrectinib; redifferentiation
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Inhibitors may treat RAI-resistant cancers by activating RAI and providing antitumoral effects, but not all patients experience redifferentiation.
Metastatic thyroid cancers may dedifferentiate and become radioactive-iodine (RAI) resistant. A redifferentiating effect can be observed with inhibitors of the mitogen-activated protein kinase pathway in thyroid cancers with point mutation in oncogenes. This effect allows RAI reuptake that may lead to a therapeutic effect different from the antitumoral effect of the inhibitor. The potential redifferentiating effect of inhibitors targeting oncogenic fusion-genes was suggested by one adult and one pediatric patient using larotrectinib in NTRK-rearranged tumors. We report on three consecutive adult patients with metastatic RAI-resistant NTRK-rearranged thyroid cancer who received larotrectinib for disease progression and for whom the redifferentiating effect was examined. Larotrectinib-induced RAI reuptake in all or part of the metastatic disease for two patients and no reuptake was noted for the other patient. We demonstrate that redifferentiation of NTRK-rearranged RAI-resistant thyroid cancer with larotrectinib may exist but does not occur in all patients.
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