Impairing energy metabolism in solid tumors through agents targeting oncogenic signaling pathways
Impairing energy metabolism in solid tumors through agents targeting oncogenic signaling pathways
复制标题
DOI：
10.1016/j.bcp.2018.03.006
复制
发表时间：
2018-05-01
影响因子：
5.8
通讯作者：
Alfieri, Roberta
中科院分区：
文献类型：
--
作者：
Fumarola, Claudia;Petronini, Pier Giorgio;Alfieri, Roberta
细胞代谢重编程是癌症的主要特征之一，许多驱动促癌信号的致癌途径也驱动着代谢的改变。本文综述了近年来癌基因靶向药物在不同实体肿瘤中作为潜在的去调节代谢调节剂的应用。许多最初设计用于抑制特定靶点的药物后来被证明具有不同的作用，涉及细胞代谢，这可能有助于这些药物抑制生长活性的机制。新陈代谢重新编程也可能是癌细胞逃离靶向药物的选择压力并产生抗药性的一种方式。在这里，我们讨论了靶向代谢如何成为克服这种耐药性的一种新的有效策略。最后，越来越多的证据表明，癌症代谢重排可能对肿瘤浸润性免疫细胞产生深远影响。通过癌基因靶向药物调控肿瘤代谢途径，不仅可以为淋巴细胞的正常激活恢复更有利的条件，而且可以增加记忆T细胞的持久性，从而提高免疫监测的效果。
Cell metabolic reprogramming is one of the main hallmarks of cancer and many oncogenic pathways that drive the cancer-promoting signals also drive the altered metabolism.This review focuses on recent data on the use of oncogene-targeting agents as potential modulators of deregulated metabolism in different solid cancers. Many drugs, originally designed to inhibit a specific target, then have turned out to have different effects involving also cell metabolism, which may contribute to the mechanisms underlying the growth inhibitory activity of these drugs. Metabolic reprogramming may also represent a way by which cancer cells escape from the selective pressure of targeted drugs and become resistant. Here we discuss how targeting metabolism could emerge as a new effective strategy to overcome such resistance.Finally, accumulating evidence indicates that cancer metabolic rewiring may have profound effects on tumor infiltrating immune cells. Modulating cancer metabolic pathways through oncogene-targeting agents may not only restore more favorable conditions for proper lymphocytes activation, but also increase the persistence of memory T cells, thereby improving the efficacy of immune-surveillance.