BRAF突变型甲状腺癌靶向治疗耐药的研究进展

Advances in research on resistance to targeted therapy in BRAF-mutant thyroid cancer

甲状腺癌作为最常见的内分泌恶性肿瘤,发病率逐年增加,但绝大多数亚型经过传统手术、促甲状腺激素(TSH)抑制治疗和131 I治疗后,预后好。随着现代医学的进步发展,对于少数传统治疗效果不佳的甲状腺癌,分子诊断及靶向治疗使甲状腺癌的治疗手段得到进一步的丰富,其中BRAF突变在甲状腺癌中广泛存在,但其对131 I治疗常常表现出原发性耐药或反应不佳。BRAF突变的靶向药物导致原发或继发耐药的因素可能包括,耐药克隆的扩张、相关通路的激活、内在突变的发生或新的遗传及表观遗传的改变等。本文将对BRAF突变型甲状腺癌靶向治疗耐药的研究进展做一综述。

As the most common endocrine malignant tumor,the incidence rate of thyroid cancer is increasing year by year.However,the vast majority of subtypes have a good prognosis after traditional surgery,TSH suppression therapy and 131 I treatment.With the progressive development of modern medicine,for a few thyroid cancers with poor effects of traditional treatment,molecular diagnosis and targeted therapy have further enriched the therapeutic means of thyroid cancer,in which BRAF mutation is widely present in thyroid cancer,but it often shows primary resistance or poor response to 131 I therapy.The factors leading to primary or secondary resistance to targeted drugs with BRAF mutation may include genomic instability,expansion of resistant clones,occurrence of intrinsic mutations,or novel genetic and epigenetic alterations.In this article,we will review the research progress in targeted therapy resistance in BRAF-mutant thyroid cancer.