Rewiring of mitochondrial metabolism in therapy-resistant cancers: permanent and plastic adaptations.
Rewiring of mitochondrial metabolism in therapy-resistant cancers: permanent and plastic adaptations.
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DOI：
10.3389/fcell.2023.1254313
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发表时间：
2023
影响因子：
5.5
通讯作者：
Echeverria, Gloria V.
中科院分区：
文献类型：
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作者：
Pendleton, Katherine E.;Wang, Karen;Echeverria, Gloria V.
肿瘤细胞代谢的失调被广泛认为是“癌症的标志”。肿瘤细胞遇到的许多选择性压力，例如暴露于抗癌治疗，转移级联的导航以及与肿瘤微环境的通信，可以引起肿瘤细胞代谢的进一步重新布线。此外，表型可塑性最近被认为是一种新兴的“癌症标志”。线粒体是动态细胞器和代谢的中心枢纽，其在癌症中的作用一直是众多研究的主要焦点。重要的是，正在开发针对线粒体的治疗方法。有趣的是，塑料（即，可逆的）和永久的（即，稳定）的代谢适应性变化。了解这些机制的可塑性或永久性对于设计代谢靶向治疗的启动、持续时间和顺序性质至关重要。在这篇综述中，我们比较了永久性和可塑性线粒体机制驱动治疗阻力。我们还讨论了治疗诱导的代谢适应的实验模型，针对永久性和可塑性代谢状态的治疗意义，以及代谢适应的临床意义。虽然代谢适应的可塑性可以使有效的治疗具有挑战性，但了解这些可塑性表型背后的机制可能会导致有希望的临床干预，最终将导致更好的癌症患者的整体护理。
Deregulation of tumor cell metabolism is widely recognized as a “hallmark of cancer.” Many of the selective pressures encountered by tumor cells, such as exposure to anticancer therapies, navigation of the metastatic cascade, and communication with the tumor microenvironment, can elicit further rewiring of tumor cell metabolism. Furthermore, phenotypic plasticity has been recently appreciated as an emerging “hallmark of cancer.” Mitochondria are dynamic organelles and central hubs of metabolism whose roles in cancers have been a major focus of numerous studies. Importantly, therapeutic approaches targeting mitochondria are being developed. Interestingly, both plastic (i.e., reversible) and permanent (i.e., stable) metabolic adaptations have been observed following exposure to anticancer therapeutics. Understanding the plastic or permanent nature of these mechanisms is of crucial importance for devising the initiation, duration, and sequential nature of metabolism-targeting therapies. In this review, we compare permanent and plastic mitochondrial mechanisms driving therapy resistance. We also discuss experimental models of therapy-induced metabolic adaptation, therapeutic implications for targeting permanent and plastic metabolic states, and clinical implications of metabolic adaptations. While the plasticity of metabolic adaptations can make effective therapeutic treatment challenging, understanding the mechanisms behind these plastic phenotypes may lead to promising clinical interventions that will ultimately lead to better overall care for cancer patients.
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DOI：
10.1186/s13058-016-0740-2
发表时间：
2016-08-11
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Bussard KM;Mutkus L;Stumpf K;Gomez-Manzano C;Marini FC
通讯作者：
Marini FC
影响因子：
11.4
作者：
Choi, Hae-Ji;Jhe, Yoo-Lim;Cheong, Jae-Ho
通讯作者：
Cheong, Jae-Ho
影响因子：
5.6
作者：
通讯作者：
--
影响因子：
2
作者：
Abdelrahman, Aziza E.;Rashed, Hayam E.;Matar, Ihab
通讯作者：
Matar, Ihab
影响因子：
9
作者：
通讯作者：
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