胰腺导管腺癌（PDAC）带来了重大的临床挑战，通常表现为无法切除且活检选择有限。在这里，我们表明循环肿瘤细胞 (CTC) 提供了一种有前途的替代方案，作为“液体活检”，能够生成体外 3D 模型和高度侵袭性的体内模型，用于高级 PDAC 的功能和分子研究。在检索到的 CTC 库（中值 65 个 CTC/5 mL）中，我们鉴定了一个 CXCR4 CTC 子集（中值含量 8.9%），其表现出高度的干性和代谢特征，让人想起循环癌症干细胞。通过综合分析，我们阐明了 CTC 衍生模型对于识别潜在靶点和指导治疗策略的重要性。对干性靶向化合物的筛选发现硬脂酰辅酶 A 去饱和酶 (SCD1) 是高级 PDAC 的一个有希望的靶标。这些结果强调了 CTC 衍生模型在发现治疗途径并最终推进 PDAC 个性化护理方面的关键作用。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Pancreatic ductal adenocarcinoma (PDAC) poses significant clinical challenges, often presenting as unresectable with limited biopsy options. Here, we show that circulating tumor cells (CTCs) offer a promising alternative, serving as a "liquid biopsy" that enables the generation of in vitro 3D models and highly aggressive in vivo models for functional and molecular studies in advanced PDAC. Within the retrieved CTC pool (median 65 CTCs/5 mL), we identify a subset (median content 8.9%) of CXCR4+ CTCs displaying heightened stemness and metabolic traits, reminiscent of circulating cancer stem cells. Through comprehensive analysis, we elucidate the importance of CTC-derived models for identifying potential targets and guiding treatment strategies. Screening of stemness-targeting compounds identified stearoyl-coenzyme A desaturase (SCD1) as a promising target for advanced PDAC. These results underscore the pivotal role of CTC-derived models in uncovering therapeutic avenues and ultimately advancing personalized care in PDAC.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.