间质性肺疾病（ILD）是许多分子靶向抗癌药物常见的严重不良事件。 ILD 的发展显着降低患者的生活质量并导致治疗停止。由于ILD的发生也与治疗效果相关，因此建立ILD的预测策略非常重要。我们重点关注信号转导和转录激活因子3（STAT3）作为分子靶向药物诱导ILD的重要机制因素。我们的研究旨在建立基于机制的 ILD 预测策略；因此，我们研究了这样的假设：STAT3的基因多态性是哺乳动物雷帕霉素靶点（mTOR）抑制剂诱导的ILD发病率的预测因素，mTOR是一类与ILD发病率较高相关的分子靶向药物。我们的临床研究清楚地表明，与其他基因型的患者相比，STAT3 -1697C>G G 等位基因纯合基因型的患者由 mTOR 抑制剂诱发 ILD 的发生率显着更高。与携带其他基因型的患者相比，G等位基因纯合基因型患者的ILD累积发生率显着更高。此外，我们的体外研究表明，在携带 G 等位基因纯合基因型的肺泡上皮细胞系中，mTOR 抑制剂可诱导上皮间质转化 (EMT)，这是组织纤维化的一个前期过程，该基因型与ILD 的风险较高。我们的研究为分子靶向药物诱导的 ILD 的发展提供了一种新的预测策略。

Interstitial lung disease (ILD) is a serious adverse event common to many molecular targeted anticancer drugs. The development of ILD significantly reduces the QOL of patients and results in treatment discontinuation. Because the development of ILD is also associated with therapeutic efficacy, the establishment of prediction strategies for ILD is important. We have focused on signal transducer and activator of transcription 3 (STAT3) as an important mechanistic factor in ILD induced by molecular targeted drugs. Our study aimed to establish mechanism-based ILD prediction strategies; therefore, we investigated the hypothesis that a genetic polymorphism in STAT3 is a predictive factor of the incidence of ILD induced by mammalian target of rapamycin (mTOR) inhibitors, a class of molecular targeted drugs associated with a higher incidence of ILD. Our clinical study clearly demonstrated that the rate of ILD induced by mTOR inhibitors was significantly higher in patients with the G allele homozygous genotype of STAT3 -1697C>G compared with those with other genotypes. The cumulative incidence of ILD in patients with the G allele homozygous genotype was significantly higher compared with that in patients carrying other genotypes. Furthermore, our in vitro study indicated that the epithelial-to-mesenchymal transition (EMT), a pre-process of tissue fibrosis, was induced by an mTOR inhibitor in lung alveolar epithelial cell lines carrying the G allele homozygous genotype which was associated with a higher risk of ILD. Our study provided a novel predictive strategy for the development of ILD induced by molecular targeted drugs.