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免疫缺陷小鼠人源肿瘤异种移植为研究和药物开发提供了先进的真实肿瘤模型——对人类癌症的鼠模型的再审视。

Human cancer xenografts in immunocompromised mice provide an advanced genuine tumor model for research and drug development-A revisit of murine models for human cancers.

机构信息

Phycin, LLC., 4539 Metropolitan Court, Frederick, MD 21704, United States of America.

出版信息

Biochim Biophys Acta Gen Subj. 2021 Aug;1865(8):129929. doi: 10.1016/j.bbagen.2021.129929. Epub 2021 May 12.

Abstract

Molecular and cell biology studies have proven that human cancers are an enormously heterogenous disease, even if they originate from the same organ and tissue with identical morphological characteristics. Cancer cells in tumors from different individuals exhibit somewhat different characteristics on multiple levels, such as with respect to 1) their genetic polymorphism; 2) epigenetic mechanisms; 3) group gene activation/inactivation; 4) cell metabolism behavior; 5) aberrant incomplete terminal differentiation; 6) proliferative potential; and 7) hierarchical structure. These multiple parameters and their different combinations determine the biological characteristics of the cancer cells and their malignant/metastatic manifestations. With progress in medical research, numerous unique vulnerable targets of cancer cells have been identified from different tumors. Modern anti-cancer drug development focuses on target-based cancer cell inhibition and elimination have greatly improved the outcome of patients with some specific cancers. The murine model of human cancer has proven to be an essential procedure for the evaluation of drug efficacy in mammalian and a key link in transferring anti-cancer drug from laboratory to clinics. As classical murine cancer xenograft models with different human cancer cell lines display limited value for personalized precision medicine, creating a complete human xenograft cancer bank with all levels of abnormalities in mice has become desperately needed. This article is a review of the pros and cons of different human x murine cancer models and an attempt to find a more suitable model for the study and discovery of new anti-cancer drugs and different combination therapies in this small animal model.

摘要

分子和细胞生物学研究已经证明,人类癌症是一种极其异质性的疾病,即使它们起源于同一器官和组织,具有相同的形态学特征。不同个体肿瘤中的癌细胞在多个层面上表现出略有不同的特征,例如:1)遗传多态性;2)表观遗传机制;3)基因簇激活/失活;4)细胞代谢行为;5)异常不完全终末分化;6)增殖潜能;和 7)层次结构。这些多个参数及其不同组合决定了癌细胞的生物学特征及其恶性/转移表现。随着医学研究的进展,从不同肿瘤中已经鉴定出许多独特的癌细胞脆弱靶点。现代抗癌药物的开发侧重于基于靶点的癌细胞抑制和消除,这极大地改善了一些特定癌症患者的预后。人类癌症的鼠模型已被证明是评估哺乳动物中药物疗效的必要程序,也是将抗癌药物从实验室转移到临床的关键环节。由于具有不同人癌细胞系的经典鼠异种移植模型对个性化精准医学的价值有限,因此在小鼠中创建具有所有异常层次的完整人异种移植癌症库已变得迫切需要。本文综述了不同人-鼠癌症模型的优缺点,并试图在这种小动物模型中找到更适合研究和发现新型抗癌药物和不同联合疗法的模型。

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