Department of Pathology, University of Michigan, Ann Arbor, Michigan, 48109; email:
Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065; email:
Annu Rev Pathol. 2017 Jan 24;12:515-545. doi: 10.1146/annurev-pathol-012615-044329. Epub 2016 Dec 21.
Next-generation sequencing has substantially enhanced our understanding of the genetics of primary brain tumors by uncovering several novel driver genetic alterations. How many of these genetic modifications contribute to the pathogenesis of brain tumors is not well understood. An exciting paradigm emerging in cancer biology is that oncogenes actively reprogram cellular metabolism to enable tumors to survive and proliferate. We discuss how some of these genetic alterations in brain tumors rewire metabolism. Furthermore, metabolic alterations directly impact epigenetics well beyond classical mechanisms of tumor pathogenesis. Metabolic reprogramming in brain tumors is also influenced by the tumor microenvironment contributing to drug resistance and tumor recurrence. Altered cancer metabolism can be leveraged to noninvasively image brain tumors, which facilitates improved diagnosis and the evaluation of treatment effectiveness. Many of these aspects of altered metabolism provide novel therapeutic opportunities to effectively treat primary brain tumors.
下一代测序技术通过揭示几种新的驱动基因突变，极大地提高了我们对原发性脑肿瘤遗传学的认识。这些基因改变中有多少有助于脑瘤的发病机制尚不清楚。癌症生物学中一个令人兴奋的范例是，癌基因积极重塑细胞代谢，使肿瘤能够存活和增殖。我们讨论了脑肿瘤中的一些这些遗传改变如何重新布线代谢。此外，代谢改变直接影响表观遗传学，远远超出肿瘤发病机制的经典机制。脑瘤中的代谢重编程也受到肿瘤微环境的影响，导致耐药性和肿瘤复发。改变的癌症代谢可以被利用来无创地成像脑肿瘤，这有助于改善诊断和评估治疗效果。改变的代谢的许多这些方面提供了新的治疗机会，以有效地治疗原发性脑肿瘤。
