Navarro Carla, Ortega Ángel, Santeliz Raquel, Garrido Bermary, Chacín Maricarmen, Galban Néstor, Vera Ivana, De Sanctis Juan Bautista, Bermúdez Valmore
Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela.
Universidad Simón Bolívar, Facultad de Ciencias de la Salud, Barranquilla 080002, Colombia.
Pharmaceutics. 2022 Jun 19;14(6):1303. doi: 10.3390/pharmaceutics14061303.
The constant changes in cancer cell bioenergetics are widely known as metabolic reprogramming. Reprogramming is a process mediated by multiple factors, including oncogenes, growth factors, hypoxia-induced factors, and the loss of suppressor gene function, which support malignant transformation and tumor development in addition to cell heterogeneity. Consequently, this hallmark promotes resistance to conventional anti-tumor therapies by adapting to the drastic changes in the nutrient microenvironment that these therapies entail. Therefore, it represents a revolutionary landscape during cancer progression that could be useful for developing new and improved therapeutic strategies targeting alterations in cancer cell metabolism, such as the deregulated mTOR and PI3K pathways. Understanding the complex interactions of the underlying mechanisms of metabolic reprogramming during cancer initiation and progression is an active study field. Recently, novel approaches are being used to effectively battle and eliminate malignant cells. These include biguanides, mTOR inhibitors, glutaminase inhibition, and ion channels as drug targets. This review aims to provide a general overview of metabolic reprogramming, summarise recent progress in this field, and emphasize its use as an effective therapeutic target against cancer.
癌细胞生物能量学的持续变化被广泛认为是代谢重编程。重编程是一个由多种因素介导的过程,这些因素包括癌基因、生长因子、缺氧诱导因子以及抑癌基因功能的丧失,它们除了支持细胞异质性外,还促进恶性转化和肿瘤发展。因此,这一特征通过适应这些疗法所带来的营养微环境的剧烈变化,促进了对传统抗肿瘤疗法的抗性。所以,它代表了癌症进展过程中的一个革命性局面,这可能有助于开发针对癌细胞代谢改变(如失调的mTOR和PI3K途径)的新的和改进的治疗策略。了解癌症发生和进展过程中代谢重编程潜在机制的复杂相互作用是一个活跃的研究领域。最近,新的方法正被用于有效对抗和消除恶性细胞。这些方法包括双胍类药物、mTOR抑制剂、谷氨酰胺酶抑制以及将离子通道作为药物靶点。本综述旨在对代谢重编程进行总体概述,总结该领域的最新进展,并强调其作为对抗癌症的有效治疗靶点的应用。