Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Pancreatic Cancer Heterogeneity, Candiolo Cancer Institute FPO-IRCCS, 10060 Candiolo, Turin, Italy.
Cell Rep Med. 2024 Sep 17;5(9):101692. doi: 10.1016/j.xcrm.2024.101692. Epub 2024 Aug 19.
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.
胰腺导管腺癌 (PDAC) 带来了重大的临床挑战，通常表现为不可切除，且可供选择的活检有限。在这里，我们表明循环肿瘤细胞 (CTC) 提供了一个很有前途的替代方法，作为一种“液体活检”，可以生成用于功能和分子研究的体外 3D 模型和高度侵袭性的体内模型。在回收的 CTC 池中（中位数 65 个 CTC/5 毫升），我们鉴定出了一小部分（中位数含量 8.9%）CXCR4 CTC，其表现出更高的干性和代谢特征，类似于循环肿瘤干细胞。通过全面分析，我们阐明了 CTC 衍生模型在识别潜在靶点和指导治疗策略方面的重要性。对干性靶向化合物的筛选确定硬脂酰辅酶 A 去饱和酶 (SCD1) 是晚期 PDAC 的一个有前途的靶点。这些结果强调了 CTC 衍生模型在揭示治疗途径和最终推进 PDAC 个性化治疗方面的关键作用。
