Enhanced phosphorylation of c-Jun by cisplatin treatment as a potential predictive biomarker for cisplatin response in combination with patient-derived tumor organoids.
Enhanced phosphorylation of c-Jun by cisplatin treatment as a potential predictive biomarker for cisplatin response in combination with patient-derived tumor organoids.
复制标题
顺铂治疗增强了 c-Jun 的磷酸化，作为与患者来源的肿瘤类器官相结合的顺铂反应的潜在预测生物标志物。
DOI：
10.1038/s41374-022-00827-2
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
M
中科院分区：
文献类型：
--
作者：
Tsukamoto Y;Kurogi S;Shibata T;Suzuki K;Hirashita Y;Fumoto S;Yano S;Yanagihara K;Nakada C;Mieno F;Kinoshita K;Fuchino T;Mizukami K;Ueda Y;Etoh T;Uchida T;Hanada T;Takekawa M;Daa T;Shirao K;Hironaka S;Murakami K;Inomata M;Hijiya N;M
尽管最近在测序技术和使用数百个细胞系的大规模药物筛选方面取得了进展，但基于突变的生物标志物的预测准确性仍然不足以作为癌症治疗的指导。因此，使用替代生物标志物的新型诊断方法将是非常可取的。我们假设信号分子磷酸化的敏感性特异性变化可能在这方面有用。本研究旨在开发一种结合特异性生物标志物和患者源性肿瘤类器官（PDOs）预测癌症对顺铂反应的方法，我们发现顺铂敏感细胞系或PDOs在顺铂治疗后24小时内显示出c-Jun （p-c-Jun）的磷酸化增强。我们还比较了6例匹配患者中6例PDOs对顺铂的反应与新辅助化疗（多西紫杉醇/顺铂/5-氟尿嘧啶）的治疗效果。在机制上，c-Jun的诱导与顺铂诱导的TNF信号传导部分相关。我们的数据表明，c-Jun对顺铂治疗反应的磷酸化增强可能是顺铂对特定癌症患者疗效的预测性生物标志物。
Despite recent advances in sequencing technology and large-scale drug screenings employing hundreds of cell lines, the predictive accuracy of mutation-based biomarkers is still insufficient as a guide for cancer therapy. Therefore, novel types of diagnostic methods using alternative biomarkers would be highly desirable. We have hypothesized that sensitivity-specific changes in the phosphorylation of signaling molecules could be useful in this respect. Here, with the aim of developing a method for predicting the response of cancers to cisplatin using a combination of specific biomarker(s) and patient-derived tumor organoids (PDOs), we found that cisplatin-sensitive cell lines or PDOs showed enhanced phosphorylation of c-Jun (p-c-Jun) within 24 h after cisplatin treatment. We also compared the responses of 6 PDOs to cisplatin with the therapeutic effect of neoadjuvant chemotherapy (docetaxel/cisplatin/5-fluorouracil) in 6 matched patients. Mechanistically, the c-Jun induction was partly related to TNF signaling induced by cisplatin. Our data suggest that enhanced phosphorylation of c-Jun in response to cisplatin treatment could be a predictive biomarker for the efficacy of cisplatin in selected cancer patients.