Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
Trends Mol Med. 2020 Jan;26(1):119-134. doi: 10.1016/j.molmed.2019.06.009. Epub 2019 Jul 18.
Mitochondria have emerged as important pharmacological targets because of their key role in cellular proliferation and death. In tumor tissues, mitochondria can switch metabolic phenotypes to meet the challenges of high energy demand and macromolecular synthesis. Furthermore, mitochondria can engage in crosstalk with the tumor microenvironment, and signals from cancer-associated fibroblasts can impinge on mitochondria. Cancer cells can also acquire a hybrid phenotype in which both glycolysis and oxidative phosphorylation (OXPHOS) can be utilized. This hybrid phenotype can facilitate metabolic plasticity of cancer cells more specifically in metastasis and therapy-resistance. In light of the metabolic heterogeneity and plasticity of cancer cells that had until recently remained unappreciated, strategies targeting cancer metabolic dependency appear to be promising in the development of novel and effective cancer therapeutics.
线粒体已成为重要的药理学靶点，因为它们在细胞增殖和死亡中起着关键作用。在肿瘤组织中，线粒体可以切换代谢表型，以满足高能量需求和大分子合成的挑战。此外，线粒体可以与肿瘤微环境进行交流，来自癌相关成纤维细胞的信号可以影响线粒体。癌细胞也可以获得混合表型，其中糖酵解和氧化磷酸化（OXPHOS）都可以被利用。这种混合表型可以更具体地促进癌细胞的代谢可塑性，特别是在转移和治疗耐药性方面。鉴于直到最近仍未被认识到的癌细胞代谢异质性和可塑性，针对癌症代谢依赖性的策略似乎在开发新型有效的癌症治疗方法方面很有前景。
