荷兰皇家艺术与科学学院Hans Clevers等研究人员合作完成，多部位神经内分泌肿瘤患者衍生器官组织中的药物生长依赖性和肿瘤演变分析。相关论文于2023年12月11日在线发表在《癌细胞》杂志上。

研究人员表示，神经内分泌肿瘤（NEN）包括分化良好的神经内分泌肿瘤（NET）和分化不良的神经内分泌癌（NEC）。NEN患者的治疗方案有限，部分原因是缺乏准确的模型。

研究人员从肺NET建立了患者衍生肿瘤器官组织（PDTO），并从NEC的一种未被充分研究的亚型——大细胞神经内分泌癌（LCNEC）建立了PDTO。PDTO保持了亲代肿瘤的基因表达模式、瘤内异质性和演化过程。通过假设驱动的药物敏感性分析，研究人员发现ASCL1是LCNEC对BCL-2抑制剂治疗反应的潜在生物标志物。此外，研究人员还发现了肺NET PDTO对EGF的依赖性。

与这些发现一致的是，研究人员发现在一个独立的队列中，约 50%的肺NET表达EGFR。这项研究为肺NET的一个亚群确定了一种可操作的脆弱性，并强调了这些PDTO模型的实用性。

附：英文原文

Title: Druggable growth dependencies and tumor evolution analysis in patient-derived organoids of neuroendocrine neoplasms from multiple body sites

Author: Talya L. Dayton, Nicolas Alcala, Laura Moonen, Lisanne den Hartigh, Veerle Geurts, Lise Mangiante, Lisa Lap, Antonella F.M. Dost, Joep Beumer, Sonja Levy, Rachel S. van Leeuwaarde, Wenzel M. Hackeng, Kris Samsom, Catherine Voegele, Alexandra Sexton-Oates, Harry Begthel, Jeroen Korving, Lisa Hillen, Lodewijk A.A. Brosens, Sylvie Lantuejoul, Sridevi Jaksani, Niels F.M. Kok, Koen J. Hartemink, Houke M. Klomp, Inne H.M. Borel Rinkes, Anne-Marie Dingemans, Gerlof D. Valk, Menno R. Vriens, Wieneke Buikhuisen, José van den Berg, Margot Tesselaar, Jules Derks, Ernst Jan Speel, Matthieu Foll, Lynnette Fernández-Cuesta, Hans Clevers

Issue&Volume: 2023/12/11

Abstract: Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Treatment options for patients with NENs are limited, in part due to lack of accurate models. We establish patient-derived tumor organoids (PDTOs) from pulmonary NETs and derive PDTOs from an understudied subtype of NEC, large cell neuroendocrine carcinoma (LCNEC), arising from multiple body sites. PDTOs maintain the gene expression patterns, intra-tumoral heterogeneity, and evolutionary processes of parental tumors. Through hypothesis-driven drug sensitivity analyses, we identify ASCL1 as a potential biomarker for response of LCNEC to treatment with BCL-2 inhibitors. Additionally, we discover a dependency on EGF in pulmonary NET PDTOs. Consistent with these findings, we find that, in an independent cohort, approximately 50% of pulmonary NETs express EGFR. This study identifies an actionable vulnerability for a subset of pulmonary NETs, emphasizing the utility of these PDTO models.

DOI: 10.1016/j.ccell.2023.11.007

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00398-7