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

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2024-08-16 DOI:10.1016/j.xcrm.2024.101692

Jiajia Tang, Quan Zheng, Qi Wang, Yaru Zhao, Preeta Ananthanarayanan, Chiara Reina, Berina Šabanović, Ke Jiang, Ming-Hsin Yang, Clara Csilla Meny, Huimin Wang, Mette Ø Agerbaek, Thomas Mandel Clausen, Tobias Gustavsson, Chenlei Wen, Felice Borghi, Alfredo Mellano, Elisabetta Fenocchio, Vanesa Gregorc, Anna Sapino, Thor G Theander, Da Fu, Alexandra Aicher, Ali Salanti, Baiyong Shen, Christopher Heeschen

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Abstract

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.

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CTC 衍生的胰腺癌模型可作为研究工具，适用于精准医疗方法。

胰腺导管腺癌（PDAC）给临床带来了巨大挑战，通常无法切除，活检选择有限。在这里，我们发现循环肿瘤细胞（CTCs）提供了一种很有前景的替代方法，它可以作为一种 "液体活检"，生成体外三维模型和高度侵袭性体内模型，用于晚期 PDAC 的功能和分子研究。在检索到的 CTC 库中（中位数为 65 CTCs/5 mL），我们发现了一个 CXCR4+ CTC 子集（中位数含量为 8.9%），它们显示出更强的干性和代谢特征，让人联想到循环肿瘤干细胞。通过综合分析，我们阐明了CTC衍生模型在确定潜在靶点和指导治疗策略方面的重要性。干细胞靶向化合物的筛选发现，硬脂酰辅酶A去饱和酶（SCD1）是治疗晚期PDAC的有希望的靶点。这些结果凸显了CTC衍生模型在发现治疗途径和最终推进PDAC个性化治疗方面的关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.

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