Medical Clinic and Polyclinic II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
Institute for Translational Cancer Research and Experimental Cancer Therapy, Technical University of Munich, Munich, Germany.
EMBO Mol Med. 2022 Apr 7;14(4):e14876. doi: 10.15252/emmm.202114876. Epub 2022 Feb 4.
Despite the advance and success of precision oncology in gastrointestinal cancers, the frequency of molecular-informed therapy decisions in pancreatic ductal adenocarcinoma (PDAC) is currently neglectable. We present a longitudinal precision oncology platform based on functional model systems, including patient-derived organoids, to identify chemotherapy-induced vulnerabilities. We demonstrate that treatment-induced tumor cell plasticity in vivo distinctly changes responsiveness to targeted therapies, without the presence of a selectable genetic marker, indicating that tumor cell plasticity can be functionalized. By adding a mechanistic layer to precision oncology, adaptive processes of tumors under therapy can be exploited, particularly in highly plastic tumors, such as pancreatic cancer.
尽管胃肠癌的精准肿瘤学取得了进展和成功，但目前在胰腺导管腺癌 (PDAC) 中，分子指导治疗决策的频率可以忽略不计。我们提出了一个基于功能模型系统的纵向精准肿瘤学平台，包括患者来源的类器官，以确定化疗诱导的脆弱性。我们证明了体内治疗诱导的肿瘤细胞可塑性明显改变了对靶向治疗的反应性，而没有可选择的遗传标记物的存在，表明肿瘤细胞可塑性可以被功能化。通过向精准肿瘤学添加一个机制层，可以利用治疗下肿瘤的适应性过程，特别是在高度可塑性的肿瘤中，如胰腺癌。
