利用患者来源的类器官研究乳腺癌中的分子代谢适应性。

The Use of Patient-Derived Organoids in the Study of Molecular Metabolic Adaptation in Breast Cancer.

机构信息

Laboratory of Molecular Cancer Research, School of Natural Sciences and Mathematics, Chaminade University of Honolulu, Honolulu, HI 96816, USA.

The IDeA Networks of Biomedical Research Excellence (INBRE) Program, School of Natural Sciences and Mathematics, Chaminade University, Honolulu, HI 96816, USA.

出版信息

Int J Mol Sci. 2024 Sep 29;25(19):10503. doi: 10.3390/ijms251910503.

Abstract

Around 13% of women will likely develop breast cancer during their lifetime. Advances in cancer metabolism research have identified a range of metabolic reprogramming events, such as altered glucose and amino acid uptake, increased reliance on glycolysis, and interactions with the tumor microenvironment (TME), all of which present new opportunities for targeted therapies. However, studying these metabolic networks is challenging in traditional 2D cell cultures, which often fail to replicate the three-dimensional architecture and dynamic interactions of real tumors. To address this, organoid models have emerged as powerful tools. Tumor organoids are 3D cultures, often derived from patient tissue, that more accurately mimic the structural and functional properties of actual tumor tissues in vivo, offering a more realistic model for investigating cancer metabolism. This review explores the unique metabolic adaptations of breast cancer and discusses how organoid models can provide deeper insights into these processes. We evaluate the most advanced tools for studying cancer metabolism in three-dimensional culture models, including optical metabolic imaging (OMI), matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), and recent advances in conventional techniques applied to 3D cultures. Finally, we explore the progress made in identifying and targeting potential therapeutic targets in breast cancer metabolism.

摘要

大约 13%的女性在其一生中可能会患上乳腺癌。癌症代谢研究的进展已经确定了一系列代谢重编程事件,例如葡萄糖和氨基酸摄取的改变、对糖酵解的依赖性增加,以及与肿瘤微环境 (TME) 的相互作用,所有这些都为靶向治疗提供了新的机会。然而,在传统的 2D 细胞培养中研究这些代谢网络具有挑战性,因为它们通常无法复制真实肿瘤的三维结构和动态相互作用。为了解决这个问题,类器官模型已经成为强大的工具。肿瘤类器官是三维培养物,通常源自患者组织,更准确地模拟体内实际肿瘤组织的结构和功能特性,为研究癌症代谢提供了更现实的模型。这篇综述探讨了乳腺癌独特的代谢适应性,并讨论了类器官模型如何为这些过程提供更深入的见解。我们评估了用于研究三维培养模型中癌症代谢的最先进工具,包括光学代谢成像 (OMI)、基质辅助激光解吸/电离质谱成像 (MALDI-MSI),以及传统技术在 3D 培养中的最新进展。最后,我们探讨了在鉴定和靶向乳腺癌代谢中的潜在治疗靶点方面取得的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0541/11477048/c3e0a300e7ac/ijms-25-10503-g001.jpg

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