Background/Aim: Amino acids are among the most important nutrients for supplying energy and building protein blocks in cancers. L-type amino acid transporter (LAT) 1 is known to play a critical role in cancer growth. We have completed the first-in-human phase I study using the LAT1-specific inhibitor JPH203. Patients and Methods: We evaluated plasma free amino acids (PFAAs), body mass index (BMI), and efficacy of JPH203 in patients enrolled in the phase I study. Results: LAT1-substrate PFAAs and branched chain amino acids (BCAAs) were higher in patients with biliary tract cancer (BTC) than in those with other cancers. High inhibition of uptake of LAT1-substrate PFAAs was associated with survival. BMI of more than the median was associated with disease control and survival. BCAAs tended to be associated with BMI. Conclusion: BCAAs and BMI are useful predictors of the efficacy of JPH203, which shows promising activity against BTC.

中文翻译：

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用 LAT1 抑制剂 JPH203 治疗晚期实体瘤患者的生物标志物分析

背景/目的：氨基酸是在癌症中提供能量和构建蛋白质块的最重要的营养素之一。已知 L 型氨基酸转运蛋白 (LAT) 1 在癌症生长中起关键作用。我们已经完成了使用 LAT1 特异性抑制剂 JPH203 的首次人体 I 期研究。患者和方法：我们评估了参加 I 期研究的患者的血浆游离氨基酸 (PFAA)、体重指数 (BMI) 和 JPH203 的疗效。结果：胆道癌 (BTC) 患者的 LAT1 底物 PFAA 和支链氨基酸 (BCAA) 高于其他癌症患者。对 LAT1 底物 PFAA 摄取的高度抑制与存活率相关。超过中位数的 BMI 与疾病控制和生存相关。BCAAs 往往与 BMI 相关。结论：