University of Michigan, Biointerfaces Institute, Ann Arbor, MI, United States; University of Michigan, School of Dentistry, Department of Biologic and Materials Sciences, Ann Arbor, MI, United States.
University of Virginia, School of Medicine, Department of Pathology, Charlottesville, VA, United States.
EBioMedicine. 2019 Mar;41:175-184. doi: 10.1016/j.ebiom.2019.02.011. Epub 2019 Feb 11.
Patient-derived xenograft (PDX) models have significantly enhanced cancer research, and often serve as a robust model. However, enhanced growth rate and altered pathological phenotype with serial passages have repeatedly been shown in adenoid cystic carcinoma (ACC) PDX tumors, which is a major concern.
We evaluated the fidelity of ACCs in their natural habitat by performing ACC orthotopic xenotransplantation (PDOX) in salivary glands.
Our PDOX model enabled solid tumors to integrate within the local epithelial, stromal and neuronal environment. Over serial passages, PDOX tumors maintained their stereotypic MYB-NFIB translocation, and FGFR2 and ATM point mutations. Tumor growth rate and histopathology were retained, including ACCs hallmark presentations of cribriform, tubular, solid areas and innervation. We also demonstrate that the PDOX model retains its capacity as a tool for drug testing.
Unlike the precedent PDX model, our data shows that the PDOX is a superior model for future cancer biology and therapy research. FUND: This work was supported by the National Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research (NIDCR) grants DE022557, DE027034, and DE027551.
患者来源的异种移植（PDX）模型显著促进了癌症研究，并且通常作为一种强大的模型。然而，在腺样囊性癌（ACC）PDX 肿瘤中，连续传代后肿瘤的生长速度加快和病理表型改变的情况屡有报道，这是一个主要关注点。
我们通过在唾液腺中进行腺样囊性癌的原位异种移植（PDOX）来评估 ACC 在其自然栖息地中的保真度。
我们的 PDOX 模型使实体瘤能够整合到局部上皮、基质和神经元环境中。在连续传代过程中，PDOX 肿瘤保持其典型的 MYB-NFIB 易位以及 FGFR2 和 ATM 点突变。肿瘤的生长速度和组织病理学特征得以保留，包括 ACC 的筛状、管状、实体区域和神经支配等特征。我们还证明了 PDOX 模型保留了作为药物测试工具的能力。
与先前的 PDX 模型不同，我们的数据表明 PDOX 是未来癌症生物学和治疗研究的更优模型。
这项工作得到了美国国立卫生研究院（NIH）/国家牙科和颅面研究所（NIDCR）授予的 DE022557、DE027034 和 DE027551 资助。
