Schulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, MN, USA.
EMBO Mol Med. 2022 Apr 7;14(4):e15707. doi: 10.15252/emmm.202215707. Epub 2022 Mar 14.
Standard-of-care regimens for pancreatic ductal adenocarcinoma (PDAC) include a combination of chemotherapies, which are associated with toxicity and eventually tumor resistance. The lack of relevant tool to identify and evaluate new therapies in PDAC necessitates the search for a model, especially for cases with treatment resistance to standard of care. In the study from Peschke et al (2022), they describe a longitudinal platform to identify drug-induced vulnerabilities following standard-of-care chemotherapy treatment using patient-derived organoids (PDOs) providing an opportunity to predict therapeutic response and define new treatment vulnerability induced by standard of care. Previously, tumor resistance to chemotherapy has typically been described as selection for resistant tumor cell populations. However, Peschke et al (2022) demonstrated that PDAC cells seemed to acquire resistance not only through genetic changes, but also through modifications in cellular plasticity leading to gene expression and metabolism changes. Thus, the study supports this type of platform for the identification of new therapeutic targets following standard-of-care treatments in PDAC.
用于胰腺导管腺癌（PDAC）的标准治疗方案包括联合化疗，这与毒性有关，最终还会导致肿瘤耐药。缺乏用于识别和评估 PDAC 新疗法的相关工具，因此需要寻找一种模型，特别是对于对标准治疗有耐药性的病例。在 Peschke 等人（2022）的研究中，他们描述了一种纵向平台，用于使用患者来源的类器官（PDO）来识别标准化疗治疗后药物诱导的脆弱性，从而有机会预测治疗反应并确定由标准治疗引起的新的治疗脆弱性。以前，通常将肿瘤对化疗的耐药性描述为对耐药肿瘤细胞群体的选择。然而，Peschke 等人（2022）表明，PDAC 细胞似乎不仅通过遗传变化获得耐药性，而且还通过细胞可塑性的改变导致基因表达和代谢变化而获得耐药性。因此，该研究支持在 PDAC 中使用这种平台来识别标准治疗后新的治疗靶点。
