Opinion|Videos|July 15, 2026
Emerging Targets and Resistance Mechanisms in Advanced Thyroid Cancer
Lori Wirth, MD, highlights future directions in the treatment of radioactive iodine–refractory differentiated thyroid cancer, emphasizing novel targets and mechanisms of resistance.
Episodes in this series
Lori Wirth, MD, highlights future directions in the treatment of radioactive iodine–refractory differentiated thyroid cancer, emphasizing novel targets and mechanisms of resistance. Ongoing clinical trials are exploring therapies directed at RAS mutations, which are common in follicular thyroid cancer, though no pan-RAS inhibitors are currently approved. Additionally, next-generation MAP kinase pathway inhibitors are under investigation to address tumors driven by non-V600E BRAF alterations, including BRAF fusions that are not responsive to current BRAF-targeted therapies. Another critical challenge is acquired resistance to gene-specific inhibitors such as RET and NTRK-targeted agents. Molecular profiling through repeat biopsy or circulating tumor DNA testing can identify resistance mechanisms, but therapeutic strategies remain complex due to heterogeneous and overlapping alterations. These unmet needs underscore the importance of continued research to expand targeted treatment options and improve long-term outcomes.
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