Abstract：
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are implicated in various cancers, including those of the lung and thyroid. The prevalence of NTRK fusions is 0.1 to 0.3% in non-small cell lung cancer (NSCLC) and as high as 26% in pediatric papillary thyroid carcinoma. Detection methods include immunohistochemistry, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, and next-generation sequencing. Management of NTRK fusion-positive lung cancer primarily involves targeted therapies, notably the tyrosine receptor kinase (TRK) inhibitors larotrectinib and entrectinib. Both agents demonstrate high response rates and durable disease control, particularly in metastatic adenocarcinoma of the lung. They are preferred as first-line treatments because of their efficacy over immunotherapy. Possible adverse events include dizziness, weight gain, neuropathy-like pain, and liver enzyme elevation. Larotrectinib and entrectinib also produce robust and durable responses in NTRK fusion-positive thyroid cancer that is refractory to radioactive iodine. Second-generation TRK inhibitors that have been designed to overcome acquired resistance are under investigation.
摘要：
神经营养酪氨酸受体激酶（NTRK）基因融合与各种癌症有关，包括肺和甲状腺。在非小细胞肺癌（NSCLC）中，NTRK融合的患病率为0.1％至0.3％，在小儿乳头状甲状腺癌中高达26％。检测方法包括免疫组织化学，荧光原位杂交,逆转录聚合酶链反应，和下一代测序。NTRK融合阳性肺癌的治疗主要涉及靶向治疗，特别是酪氨酸受体激酶（TRK）抑制剂larotrectinib和entrectinib。两种药物都显示出高反应率和持久的疾病控制，特别是在转移性肺腺癌中。它们优选作为一线治疗,因为它们优于免疫疗法。可能的不良事件包括头晕，体重增加,神经病样疼痛,和肝酶升高。Larotrectinib和entrectinib还在NTRK融合阳性甲状腺癌中产生稳健而持久的反应，该反应对放射性碘是难治性的。旨在克服获得性抗性的第二代TRK抑制剂正在研究中。
