CTC-derived pancreatic cancer models serve as research tools and are suitable for precision medicine approaches

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. [Display omitted] •A CTC platform for retrieving CTCs from patients with pancreatic cancer was developed•The obtained CTCs contain a rare subset of CXCR4+ metastatic cancer stem cells•CTC-derived cultures from patients with advanced pancreatic cancer could be established•Drug screening utilizing these models identified SCD1 as a potential target Tang et al. introduce a malaria protein VAR2-based platform for retrieving circulating tumor cells from patients with pancreatic cancer. The obtained high numbers of circulating tumor cells facilitated the creation of in vitro and in vivo models suitable for drug screening and identified stearoyl-coenzyme A desaturase (SCD1) as a potential therapeutic target.