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人类黑色素瘤皮肤癌模型:迈向药物测试与靶向治疗的一步。

Human Melanoma Skin Cancer Models: A Step Towards Drug Testing & Target Therapy.

作者信息

Barghian Zarnaghi Behnaz, Barghian Zarnaghi Elnaz, Nilforoushzadeh Mohammad Ali, Roshanzamir Naeimeh, Amirkhani Mohammad Amir, Mollapour Sisakht Mahsa

机构信息

Stem Cell and Regenerative Medicine Innovation Center, Tehran University of Medical Sciences, Tehran, Iran.

Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Stem Cell Rev Rep. 2025 Apr 8. doi: 10.1007/s12015-025-10870-3.

DOI:10.1007/s12015-025-10870-3
PMID:40198476
Abstract

Melanoma is one of the most aggressive types of solid cancer, originating in melanocytes. Due to its complex and heterogeneous nature, it can respond very differently to treatment. For many years, researchers have used standard two-dimensional cell cultures to evaluate drug efficacy and understand the cellular and molecular biology of this disease, but 2D cultures have limitations compared to 3D cultures when it comes to mimicking the tumor microenvironment in the body. Rodent models are often used to understand melanoma progression and develop new effective treatments, but they do not accurately represent human physiology. Ex vivo modelling of melanoma could significantly improve our understanding and predict treatment outcomes. Efforts have been directed toward developing reliable models that accurately mimic melanoma in its appropriate tissue environment, including spheroid formation, tumor organoids, bio-printed tissue constructs, and microfluidic devices. This review provides a comprehensive exploration of 3D models used in drug screening for targeted therapy in melanoma by screening 120 studies and critically discussing 22 key research publications. Moreover, we provide details of drug screening accuracy and therapeutic efficacy of melanoma 3D models and identify current challenges to propose future directions for enhancing 3D model-based drug screening.

摘要

黑色素瘤是最具侵袭性的实体癌类型之一,起源于黑素细胞。由于其性质复杂且异质性强,它对治疗的反应可能非常不同。多年来,研究人员一直使用标准的二维细胞培养来评估药物疗效并了解这种疾病的细胞和分子生物学,但在模拟体内肿瘤微环境方面,二维培养与三维培养相比存在局限性。啮齿动物模型常被用于了解黑色素瘤的进展并开发新的有效治疗方法,但它们并不能准确代表人体生理学。黑色素瘤的体外建模可以显著提高我们的理解并预测治疗结果。人们一直在努力开发可靠的模型,这些模型能在适当的组织环境中准确模拟黑色素瘤,包括球体形成、肿瘤类器官、生物打印组织构建体和微流控装置。本综述通过筛选120项研究并批判性地讨论22篇关键研究出版物,全面探讨了用于黑色素瘤靶向治疗药物筛选的三维模型。此外,我们提供了黑色素瘤三维模型的药物筛选准确性和治疗效果的详细信息,并确定了当前的挑战,以提出增强基于三维模型的药物筛选的未来方向。

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Human Melanoma Skin Cancer Models: A Step Towards Drug Testing & Target Therapy.人类黑色素瘤皮肤癌模型:迈向药物测试与靶向治疗的一步。
Stem Cell Rev Rep. 2025 Apr 8. doi: 10.1007/s12015-025-10870-3.
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本文引用的文献

1
Biofabrication and Monitoring of a 3D Printed Skin Model for Melanoma.3D 打印皮肤模型用于黑色素瘤的生物制造和监测。
Adv Healthc Mater. 2024 Oct;13(27):e2401136. doi: 10.1002/adhm.202401136. Epub 2024 Jul 11.
2
Immune escape and metastasis mechanisms in melanoma: breaking down the dichotomy.黑色素瘤中的免疫逃逸和转移机制:打破二分法。
Front Immunol. 2024 Feb 14;15:1336023. doi: 10.3389/fimmu.2024.1336023. eCollection 2024.
3
Generation of 3D melanoma models using an assembloid-based approach.使用基于组装体的方法生成三维黑色素瘤模型。
Acta Biomater. 2024 Apr 1;178:93-110. doi: 10.1016/j.actbio.2024.02.023. Epub 2024 Feb 19.
4
Scaffold-based 3D cell culture models in cancer research.基于支架的 3D 细胞培养模型在癌症研究中的应用。
J Biomed Sci. 2024 Jan 14;31(1):7. doi: 10.1186/s12929-024-00994-y.
5
A human mucosal melanoma organoid platform for modeling tumor heterogeneity and exploring immunotherapy combination options.用于模拟肿瘤异质性和探索免疫治疗联合方案的人黏膜黑色素瘤类器官平台。
Sci Adv. 2023 Oct 27;9(43):eadg6686. doi: 10.1126/sciadv.adg6686.
6
Oncolytic viral therapy: a review and promising future directions.溶瘤病毒治疗:综述及有前景的未来方向。
J Neurosurg. 2023 Aug 25;140(2):319-327. doi: 10.3171/2023.6.JNS23243. Print 2024 Feb 1.
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A 3-dimensional histology computer model of malignant melanoma and its implications for digital pathology.恶性黑色素瘤的三维组织学计算机模型及其对数字病理学的意义。
Eur J Cancer. 2023 Nov;193:113294. doi: 10.1016/j.ejca.2023.113294. Epub 2023 Aug 18.
8
Patient-derived melanoma organoid models facilitate the assessment of immunotherapies.患者来源的黑色素瘤类器官模型有助于评估免疫疗法。
EBioMedicine. 2023 Jun;92:104614. doi: 10.1016/j.ebiom.2023.104614. Epub 2023 May 23.
9
3D melanoma spheroid model for the development of positronium biomarkers.用于正电子素生物标志物开发的 3D 黑色素瘤球体模型。
Sci Rep. 2023 May 11;13(1):7648. doi: 10.1038/s41598-023-34571-4.
10
Microfluidics guided by deep learning for cancer immunotherapy screening.基于深度学习的癌症免疫疗法筛选的微流控技术。
Proc Natl Acad Sci U S A. 2022 Nov 16;119(46):e2214569119. doi: 10.1073/pnas.2214569119. Epub 2022 Nov 7.