Three-Dimensional Tumor Models to Study Cancer Stemness-Mediated Drug Resistance

IF 2.3 4区医学 Q3 BIOPHYSICS

Cellular and molecular bioengineering Pub Date : 2024-02-21 DOI:10.1007/s12195-024-00798-y

Astha Lamichhane, Hossein Tavana

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Abstract

Solid tumors often contain genetically different populations of cancer cells, stromal cells, various structural and soluble proteins, and other soluble signaling molecules. The American Cancer society estimated 1,958,310 new cancer cases and 609,820 cancer deaths in the United States in 2023. A major barrier against successful treatment of cancer patients is drug resistance. Gain of stem cell-like states by cancer cells under drug pressure or due to interactions with the tumor microenvironment is a major mechanism that renders therapies ineffective. Identifying approaches to target cancer stem cells is expected to improve treatment outcomes for patients. Most of our understanding of drug resistance and the role of cancer stemness is from monolayer cell cultures. Recent advances in cell culture technologies have enabled developing sophisticated three-dimensional tumor models that facilitate mechanistic studies of cancer drug resistance. This review summarizes the role of cancer stemness in drug resistance and highlights the various tumor models that are used to discover the underlying mechanisms and test potentially novel therapeutics.

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研究癌症干细胞介导的抗药性的三维肿瘤模型

实体瘤通常包含不同基因的癌细胞、基质细胞、各种结构蛋白和可溶性蛋白以及其他可溶性信号分子。据美国癌症协会估计，2023 年美国将新增 1,958,310 例癌症病例和 609,820 例癌症死亡病例。抗药性是成功治疗癌症患者的一大障碍。癌细胞在药物压力下或因与肿瘤微环境相互作用而获得干细胞样状态，是导致疗法无效的主要机制。找到针对癌症干细胞的方法有望改善患者的治疗效果。我们对耐药性和癌症干细胞作用的了解大多来自单层细胞培养。近来细胞培养技术的进步使我们能够建立复杂的三维肿瘤模型，促进癌症耐药性的机理研究。本综述总结了癌症干细胞在耐药性中的作用，并重点介绍了用于发现潜在机制和测试潜在新型疗法的各种肿瘤模型。

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来源期刊

Cellular and molecular bioengineering 生物-生物物理

CiteScore

5.60

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.