The NTRK genes encode the tropomyosin-related receptor tyrosine kinases TrkA, TrkB and TrkC. TRK receptors regulate the proliferation, differentiation, and survival of many neuronal and non-neuronal glial cells during embryogenesis, thus playing a critical role in synaptic plasticity and the development of nociceptive pathways. Recurrent genomic alterations in NTRK genes, typically fusions involving the 3′ region encoding the kinase domain juxtaposed to 5′ sequences from numerous partner genes, occur at a low frequency in a wide diversity of adult and pediatric cancers. The contributions of the resulting constitutively activated kinase to oncogenesis and cancer progression are being elucidated. Larotrectinib and entrectinib are potent first-generation TRK inhibitors with IC₅₀ values in the nanomolar range across cancer cell lines harboring NTRK fusions. Larotrectinib is highly selective for TRK receptors, whereas entrectinib also potently inhibits ROS1 and ALK. Clinical trials of both drugs demonstrated significant and durable responses in patients with tumors harboring NTRK alterations, leading to first of its kind cancer agnostic FDA approvals in the United States for drugs targeting a genomic alteration. Unfortunately, acquired resistance inevitably develops. The second-generation TRK inhibitors selitrectinib and repotrectinib are designed to overcome known mechanisms of resistance.

该NTRK基因编码的原肌球蛋白相关的受体酪氨酸激酶的TrkA，TrkB和TrkC的。TRK 受体在胚胎发生过程中调节许多神经元和非神经元神经胶质细胞的增殖、分化和存活，从而在突触可塑性和伤害感受途径的发展中发挥关键作用。NTRK基因中反复发生的基因组改变，通常涉及编码激酶结构域的 3' 区域与来自众多伙伴基因的 5' 序列并列的融合，在各种成人和儿童癌症中以低频率发生。正在阐明由此产生的组成型活化激酶对肿瘤发生和癌症进展的贡献。Larotrectinib 和 entrectinib 是有效的第一代 TRK 抑制剂，具有 IC包含 NTRK融合的癌细胞系中有_{50 个}纳摩尔范围内的值。Larotrectinib 对 TRK 受体具有高度选择性，而 entrectinib 也有效抑制 ROS1 和 ALK。这两种药物的临床试验表明，对携带NTRK改变的肿瘤患者有显着和持久的反应，导致美国 FDA 首次批准了针对基因组改变的药物。不幸的是，获得性耐药性不可避免地产生。第二代 TRK 抑制剂 selitrectinib 和 repotrectinib 旨在克服已知的耐药机制。