PO.CL07.01 · 临床研究
以最少的PDO保留预测能力:为转移性CRC个体化治疗加速药物检测
Preserving predictive power with minimal PDOs: Accelerated drug testing for personalized therapy in metastatic CRC
该海报暂无可下载的资料
AACR 官方页面
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
复发或转移性结直肠癌(CRC)患者面临治疗选择有限、副作用显著以及在确定有效疗法方面长期延误等问题。患者来源类器官(PDO;HUB Organoids®)提供了一个临床相关平台,能够忠实地反映个体肿瘤生物学特征,从而实现个体化药物检测。然而,传统的药物筛选形式通常每孔需要数百个类器官,这限制了使用PDO在诊断或复发时指导实时治疗决策的可行性。转化速度至关重要:在转移性CRC中,在疾病进展或治疗相关毒性发生之前,选择有效疗法的窗口期很窄。传统临床前模型通常需要数周至数月,这对于指导即时患者诊疗而言太慢。为解决这一局限,我们开发了一种使用Yamaha CELL HANDLER™系统的自动化类器官处理工作流程,能够实现精确转移和基于图像的定量分析,同时每孔所需类器官数量大幅减少。与传统筛选相比,小型化使输入材料减少了96%(从每孔250个PDO减至10个PDO)。使用小型化检测测得的PDO药物敏感性与传统筛选结果高度吻合(R=0.67-0.85,p<0.03)。小型化检测中的PDO反应也与患者结局相关,包括无进展生存期(R=-0.85,p<0.01)。通过结合自动化、小型化和定量读数,该平台在保留PDO预测能力的同时,大幅减少了对类器官的需求,并缩短了周转时间。
查看英文原文 English abstract
Patients with relapsed or metastatic colorectal cancer (CRC) face limited treatment options, significant side effects, and prolonged delays in identifying effective therapies. Patient-derived organoids (PDOs; HUB Organoids®) provide a clinically relevant platform that faithfully mirrors individual tumour biology, enabling personalised drug testing. However, conventional drug screening formats typically require several hundred organoids per well, limiting the feasibility of using PDOs to guide real-time treatment decisions at diagnosis or relapse. Translational speed is critical: in metastatic CRC, there is a narrow window to select effective therapy before disease progression or treatment-related toxicity occurs. Traditional preclinical models often take weeks to months, which is too slow to inform immediate patient care. To address this limitation, we developed an automated organoid-handling workflow using the Yamaha CELL HANDLER™ system, enabling precise transfer and image-based quantification while requiring far fewer organoids per well. Miniaturisation reduced input material by 96% (from 250 to 10 PDOs per well) compared to conventional screening. Drug sensitivity of PDOs measured using the miniaturised assay closely mirrored that of conventional screening (R=0.67-0.85, p<0.03). PDO responses in the miniaturised assay also correlated with patient outcomes, including progression-free survival (R = -0.85, p < 0.01).By combining automation, miniaturisation, and quantitative readouts, this platform preserves the predictive power of PDOs, drastically reduces the need for organoids, and shortens turnaround time.
利益披露 Disclosure
Y. Abouleila, None..
R. Verkerk, None..
M. Doorn, None..
T. Voskuilen, None..
G. Harada, None..
M. Watanabe, None..
L. Smabers, None..
H. Kyan, None..
T. Kumagai, None..
Y. Hikichi, None..
R. Overmeer, None..
J. Roodhart, None..
K. Matsuno, None..
C. S. Verissimo, None..
R. G. J. Vries, None..
S. F. Boj, None.