LBPO.TB03 · 肿瘤生物学 · Late-Breaking
器官芯片：一种研究肺癌患者来源细胞辅助治疗疗效与预测的体外模型
Organ-on-Chip: An in vitro model to study the efficacy and prediction of adjuvant therapy in lung cancer patient-derived cells
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
肺癌是全球癌症相关死亡的主要原因，占癌症诊断的11.6%和癌症死亡的18.4%。非小细胞肺癌（NSCLC）占病例的85%，常由遗传学改变驱动，包括16%患者中的EGFR突变。尽管有靶向治疗，总生存率仍然很差，凸显了对更有效、个性化治疗的需求。在早期肺癌中，辅助化疗在手术后给予以降低复发，但其疗效的不确定性限制了其预测价值。能更好地在离体模拟肿瘤微环境的系统可能有助于改善对患者特异性治疗策略的识别。为解决这一问题，我们采用了类器官芯片（OoC）技术，这是一种先进的体外平台，能重现肿瘤微环境的关键特征，并已成为评估药物反应的有前景的工具。本研究旨在确定器官芯片系统是否能预测NSCLC患者来源类器官（PDO）对辅助化疗的反应。在我们的研究中，我们从NSCLC样本生成了一个包含30个患者来源类器官（PDO）的队列。这些PDO通过免疫组织化学、全外显子组测序（WES）和RNA测序进行验证，以确认其与原始肿瘤的相似性。从该队列中，我们将选择来自接受相同辅助化疗方案（顺铂+长春瑞滨）患者的PDO。将PDO单独培养或与癌症相关成纤维细胞（CAF）在芯片中共培养并处理72小时。使用活/死细胞检测测量活力。我们在作为概念验证方法学的特定患者上获得的初步结果显示，与单一培养条件相比，CAF促进了治疗耐药，表现为生存率增加50%。我们将把所选PDO队列的发现与相应患者的临床结局相关联，以评估该系统的预测能力。总之，OoC平台在建模和预测患者特异性治疗反应方面显示出强大的潜力，支持肺癌中更加个性化和有效的治疗策略。
查看英文原文 English abstract
Lung cancer is the leading cause of cancer-related deaths worldwide, accounting for 11.6% of cancer diagnoses and 18.4% of cancer mortality. Non-small cell lung cancer (NSCLC) represents 85% of cases and is often driven by genetic alterations, including EGFR mutations in 16% of patients. Despite targeted therapies, overall survival remains poor, emphasizing the need for more effective, personalized treatments. In early-stage lung cancer, adjuvant chemotherapy is given after surgery to reduce recurrence, but its variable efficacy limits its predictive value. Systems that better mimic the tumor microenvironment ex vivo may improve identification of patient-specific therapeutic strategies. To address this, we used Organoid-on-Chip (OoC) technology, an advanced in vitro platform that recreates key features of the tumor microenvironment and has emerged as a promising tool for evaluating drug responses. The aim of this study is to determine whether an organ-on-chip system can predict responses to adjuvant chemotherapy in NSCLC patient-derived organoids (PDOs). In our study, we generated a cohort of 30 patient-derived organoids (PDOs) from NSCLC sample. These PDOs were validated via immunohistochemistry, whole exome sequencing (WES), and RNA sequencing to confirm their similarity to the original tumors. From this cohort, we will select PDOs that derived from patients who received the same adjuvant chemotherapy regimen (Cisplatin + Vinorelbine). PDOs were cultured alone or co-cultured with cancer-associated fibroblasts (CAFs) in the chip and treated for 72 hours. Viability was measured using live/dead assays. Our preliminary results, on a specific patient used as proof-of-concept methodology, shows that CAFs contribute to therapy resistance compared to monoculture conditions showing an increase of survival of 50%. We will correlate the findings on the selected cohort of PDOs with the clinical outcome of the respective patient to evaluate the predictive power of the system. In conclusion, the OoC platform shows strong potential for modeling and predicting patient-specific therapy responses, supporting more personalized and effective treatment strategies in lung cancer.
利益披露 Disclosure
F. Dona, None..
N. Grkovic, None..
A. Putignano, None..
L. Terracciano, None..
D. Brascia, None..
E. Re Cecconi, None..
V. Giudici, None..
P. Bossi, None..
C. Ng, None..
G. Marulli, None..
S. Piscuoglio, None.