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患者来源异种移植物:药物开发和生物标志物发现的有价值的临床前模型。

Patient-Derived Xenografts: A Valuable Preclinical Model for Drug Development and Biomarker Discovery.

机构信息

Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia.

Department of Molecular and Translational Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, VIC, Australia.

出版信息

Methods Mol Biol. 2024;2806:19-30. doi: 10.1007/978-1-0716-3858-3_3.

DOI:10.1007/978-1-0716-3858-3_3
PMID:38676793
Abstract

Patient-derived xenografts (PDXs), established by implanting patient tumor cells into immunodeficient mice, offer a platform for faithfully replicating human tumors. They closely mimic the histopathology, genomics, and drug sensitivity of patient tumors. This chapter highlights the versatile applications of PDXs, including studying tumor biology, metastasis, and chemoresistance, as well as their use in biomarker identification, drug screening, and personalized medicine. It also addresses challenges in using PDXs in cancer research, including variations in metastatic potential, lengthy establishment timelines, stromal changes, and limitations in immunocompromised models. Despite these challenges, PDXs remain invaluable tools guiding patient treatment and advancing preclinical drug development.

摘要

患者来源异种移植(PDXs),通过将患者肿瘤细胞植入免疫缺陷小鼠中建立,为忠实地复制人类肿瘤提供了一个平台。它们非常类似于患者肿瘤的组织病理学、基因组学和药物敏感性。本章重点介绍了 PDXs 的多种应用,包括研究肿瘤生物学、转移和化疗耐药性,以及它们在生物标志物鉴定、药物筛选和个性化医学中的应用。它还讨论了在癌症研究中使用 PDXs 面临的挑战,包括转移潜力的变化、漫长的建立时间、基质变化和免疫缺陷模型的局限性。尽管存在这些挑战,但 PDXs 仍然是指导患者治疗和推进临床前药物开发的宝贵工具。

相似文献

1
Patient-Derived Xenografts: A Valuable Preclinical Model for Drug Development and Biomarker Discovery.患者来源异种移植物:药物开发和生物标志物发现的有价值的临床前模型。
Methods Mol Biol. 2024;2806:19-30. doi: 10.1007/978-1-0716-3858-3_3.
2
Patient-Derived Xenograft Models for Translational Prostate Cancer Research and Drug Development.用于前列腺癌转化研究和药物开发的患者来源异种移植模型。
Methods Mol Biol. 2024;2806:153-185. doi: 10.1007/978-1-0716-3858-3_12.
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Establishment of a platform of non-small-cell lung cancer patient-derived xenografts with clinical and genomic annotation.建立具有临床和基因组注释的非小细胞肺癌患者来源异种移植平台。
Lung Cancer. 2018 Oct;124:168-178. doi: 10.1016/j.lungcan.2018.08.008. Epub 2018 Aug 11.
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Patient-derived xenografts from non-small cell lung cancer brain metastases are valuable translational platforms for the development of personalized targeted therapy.来源于非小细胞肺癌脑转移的患者源性异种移植物是开发个体化靶向治疗的有价值的转化平台。
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本文引用的文献

1
Patient-derived xenograft models in cancer therapy: technologies and applications.癌症治疗中的患者来源异种移植模型:技术与应用。
Signal Transduct Target Ther. 2023 Apr 12;8(1):160. doi: 10.1038/s41392-023-01419-2.
2
Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases.曲妥珠单抗-德鲁替康在乳腺癌脑转移中的临床前和临床疗效。
Clin Cancer Res. 2023 Jan 4;29(1):174-182. doi: 10.1158/1078-0432.CCR-22-1138.
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Patient-derived xenograft (PDX) models, applications and challenges in cancer research.
患者来源异种移植 (PDX) 模型在癌症研究中的应用及挑战。
J Transl Med. 2022 May 10;20(1):206. doi: 10.1186/s12967-022-03405-8.
4
A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology.用于药物发现和精准肿瘤学的人乳腺癌衍生异种移植和类器官平台。
Nat Cancer. 2022 Feb;3(2):232-250. doi: 10.1038/s43018-022-00337-6. Epub 2022 Feb 24.
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Drug resistance and combating drug resistance in cancer.癌症中的耐药性与抗耐药性
Cancer Drug Resist. 2019;2(2):141-160. doi: 10.20517/cdr.2019.10. Epub 2019 Jun 19.
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The ever-increasing importance of cancer as a leading cause of premature death worldwide.癌症作为全球范围内导致过早死亡的主要原因,其重要性日益增加。
Cancer. 2021 Aug 15;127(16):3029-3030. doi: 10.1002/cncr.33587. Epub 2021 Jun 4.
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Patient-Derived Xenograft Engraftment and Breast Cancer Outcomes in a Prospective Neoadjuvant Study (BEAUTY).患者来源异种移植物植入与前瞻性新辅助研究(BEAUTY)中的乳腺癌结局。
Clin Cancer Res. 2021 Sep 1;27(17):4696-4699. doi: 10.1158/1078-0432.CCR-21-0641. Epub 2021 Jun 2.
8
Androgen receptor enhancer amplification in matched patient-derived xenografts of primary and castrate-resistant prostate cancer.雄激素受体增强子扩增在原发和去势抵抗性前列腺癌患者来源异种移植模型中的研究
J Pathol. 2021 Jun;254(2):121-134. doi: 10.1002/path.5652. Epub 2021 Mar 29.
9
Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts.在患者来源的肿瘤异种移植物的植入和传代过程中保持拷贝数谱的一致性。
Nat Genet. 2021 Jan;53(1):86-99. doi: 10.1038/s41588-020-00750-6. Epub 2021 Jan 7.
10
The Essential Factors of Establishing Patient-derived Tumor Model.建立患者来源肿瘤模型的关键因素。
J Cancer. 2021 Jan 1;12(1):28-37. doi: 10.7150/jca.51749. eCollection 2021.