Tarrado-Castellarnau Míriam, de Atauri Pedro, Cascante Marta
Department of Biochemistry and Molecular Biomedicine, Universitat de Barcelona, Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain.
Oncotarget. 2016 Sep 20;7(38):62726-62753. doi: 10.18632/oncotarget.10911.
Development of malignancy is accompanied by a complete metabolic reprogramming closely related to the acquisition of most of cancer hallmarks. In fact, key oncogenic pathways converge to adapt the metabolism of carbohydrates, proteins, lipids and nucleic acids to the dynamic tumor microenvironment, conferring a selective advantage to cancer cells. Therefore, metabolic properties of tumor cells are significantly different from those of non-transformed cells. In addition, tumor metabolic reprogramming is linked to drug resistance in cancer treatment. Accordingly, metabolic adaptations are specific vulnerabilities that can be used in different therapeutic approaches for cancer therapy. In this review, we discuss the dysregulation of the main metabolic pathways that enable cell transformation and its association with oncogenic signaling pathways, focusing on the effects of c-MYC, hypoxia inducible factor 1 (HIF1), phosphoinositide-3-kinase (PI3K), and the mechanistic target of rapamycin (mTOR) on cancer cell metabolism. Elucidating these connections is of crucial importance to identify new targets and develop selective cancer treatments that improve response to therapy and overcome the emerging resistance to chemotherapeutics.
恶性肿瘤的发展伴随着完全的代谢重编程，这与大多数癌症特征的获得密切相关。事实上，关键的致癌途径汇聚在一起，使碳水化合物、蛋白质、脂质和核酸的代谢适应动态的肿瘤微环境，赋予癌细胞选择性优势。因此，肿瘤细胞的代谢特性与未转化细胞的代谢特性显著不同。此外，肿瘤代谢重编程与癌症治疗中的耐药性有关。相应地，代谢适应是特定的脆弱点，可用于癌症治疗的不同治疗方法。在本综述中，我们讨论了促成细胞转化的主要代谢途径的失调及其与致癌信号通路的关联，重点关注c-MYC、缺氧诱导因子1（HIF1）、磷酸肌醇-3-激酶（PI3K）和雷帕霉素靶蛋白（mTOR）对癌细胞代谢的影响。阐明这些联系对于识别新靶点和开发选择性癌症治疗方法至关重要，这些方法可改善治疗反应并克服对化疗药物新出现的耐药性。
