BRAF V600E突变晚期分化型甲状腺癌治疗现状与进展OA

Differentiated thyroid carcinoma(DTC)generally has a favorable prognosis;however,approximately one-third of advanced patients progress to radioiodine-refractory DTC(RAIR-DTC),which is associated with poor survival outcomes.BRAF V600E is the most prevalent oncogenic driver mutation in thyroid cancer.It is responsible not only for the aberrant activation of the mitogen-activated protein kinase(MAPK)signaling pathway but also serves as the core mechanism for tumor dedifferentiation and iodine resistance.Currently,multi-target tyrosine kinase inhibitors(MTKIs)serve as the first-line systemic therapy for RAIR-DTC.Although MTKIs can prolong progression-free survival,their"off-target"effects frequently lead to severe cardiovascular toxicities,which impact patient compliance and quality of life.In recent years,highly selective BRAF/MEK dual inhibitors(e.g.,dabrafenib plus trametinib)have demonstrated high objective response rates and durable survival benefits in phase Ⅲ studies of RAIR-DTC,showing a more advantageous safety profile.Furthermore,targeted neoadjuvant therapy increases the opportunity for patients to achieve radical resection;meanwhile,short-term targeted blockade of the MAPK pathway can induce"redifferentiation"of thyroid cancer cells,restoring radioiodine uptake in the majority of patients.This article systematically reviews the oncogenic mechanisms of the BRAF V600E mutation and its latest clinical advancements in precision systemic therapy,neoadjuvant conversion therapy and redifferentiation therapy,aiming to provide a reference for the individualized management of thyroid cancer.