Department of Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 3525433, Israel.
Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cancer Research UK Cambridge Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge CB2 0QQ, United Kingdom.
Cold Spring Harb Perspect Med. 2024 Sep 3;14(9):a041536. doi: 10.1101/cshperspect.a041536.
With the foundation pre-laid, research in the new millennium has readily excavated and expanded upon the architectural framework laid out by Otto Warburg's seminal work in a new wave of "westward expansion," ever widening our understanding of cancer metabolism beyond the telescopic vision seen over a century ago. On this path, the unique circuitry of the cancer metabolic program has been elucidated, illuminating mutations of conserved cellular pathways implicated in tumorigenesis. Paramount among these are mutations in tricarboxylic acid cycle enzymes, succinate dehydrogenase, and fumarate hydratase, leading to deleterious accumulations in metabolic intermediates, "oncometabolites," the pilots of the disease process. In this work, we seek to reflect on the advancements in the field in recent years, updating knowledge on the exact biochemical mechanisms at the helm of the tumor, providing rationale for clinical trials currently underway, and anticipating directions for the future on this expansive frontier.
随着基础的奠定，新千年的研究在奥托·瓦尔堡开创性工作所奠定的架构框架上进行了深入挖掘和拓展，在“西进”的新浪潮中，我们对癌症代谢的理解不断拓宽，超越了一个多世纪前的望远镜视野。在这条道路上，癌症代谢程序的独特电路已经被阐明，阐明了与肿瘤发生相关的保守细胞途径的突变。其中最重要的是三羧酸循环酶、琥珀酸脱氢酶和延胡索酸水合酶的突变，导致代谢中间产物“致癌代谢物”的有害积累，这些是疾病过程的推动者。在这项工作中，我们试图反思近年来该领域的进展，更新对肿瘤核心的确切生化机制的认识，为当前正在进行的临床试验提供依据，并展望这一广阔前沿的未来方向。
