Evaluations of the molecular and pathological patterns of treatment resistance following RET selective inhibitor therapy in patients with MTC have shown (i) acquisition of resistance mutation is the primary cause of progressive disease, which can be captured by liquid biopsy, and (ii) bypass mutations of resistance may occur at a substantially higher frequency (80%) than on-target resistance mutations (101). The gene discussed is RET; the disease is medullary thyroid gland carcinoma.