Kim Michelle M, Parolia Abhijit, Dunphy Mark P, Venneti Sriram
Department of Radiation Oncology, University of Michigan Health System, University of Michigan.
Department of Pathology, University of Michigan Health System, University of Michigan, 3520E Medical Science Research Building 1, 1150 West Medical Center Drive, Ann Arbor, Michigan 48104, USA.
Nat Rev Clin Oncol. 2016 Dec;13(12):725-739. doi: 10.1038/nrclinonc.2016.108. Epub 2016 Jul 19.
The revolution in cancer genomics has uncovered a variety of clinically relevant mutations in primary brain tumours, creating an urgent need to develop non-invasive imaging biomarkers to assess and integrate this genetic information into the clinical management of patients. Metabolic reprogramming is a central hallmark of cancer, including brain tumours; indeed, many of the molecular pathways implicated in the pathogenesis of brain tumours result in reprogramming of metabolism. This relationship provides the opportunity to devise in vivo metabolic imaging modalities to improve diagnosis, patient stratification, and monitoring of treatment response. Metabolic phenomena, such as the Warburg effect and altered mitochondrial metabolism, can be leveraged to image brain tumours using techniques including PET and MRI. Moreover, genetic alterations, such as mutations affecting isocitrate dehydrogenase, are associated with unique metabolic signatures that can be detected using magnetic resonance spectroscopy. The need to translate our understanding of the molecular features of brain tumours into imaging modalities with clinical utility is growing; metabolic imaging provides a unique platform to achieve this objective. In this Review, we examine the molecular basis for metabolic reprogramming in brain tumours, and examine current non-invasive metabolic imaging strategies that can be used to interrogate these molecular characteristics with the ultimate goal of guiding and improving patient care.
癌症基因组学的革命揭示了原发性脑肿瘤中多种与临床相关的突变,这迫切需要开发非侵入性成像生物标志物,以评估这些遗传信息并将其整合到患者的临床管理中。代谢重编程是癌症(包括脑肿瘤)的一个核心特征;事实上,许多与脑肿瘤发病机制相关的分子途径都会导致代谢重编程。这种关系为设计体内代谢成像方法提供了机会,以改善诊断、患者分层和治疗反应监测。代谢现象,如瓦伯格效应和线粒体代谢改变,可利用正电子发射断层扫描(PET)和磁共振成像(MRI)等技术对脑肿瘤进行成像。此外,基因改变,如影响异柠檬酸脱氢酶的突变,与独特的代谢特征相关,可通过磁共振波谱检测到。将我们对脑肿瘤分子特征的理解转化为具有临床实用性的成像方法的需求日益增长;代谢成像提供了实现这一目标的独特平台。在本综述中,我们研究了脑肿瘤中代谢重编程的分子基础,并探讨了当前可用于探究这些分子特征的非侵入性代谢成像策略,最终目标是指导和改善患者护理。