Fahrmann Johannes F, Vykoukal Jody V, Ostrin Edwin J
Department of Clinical Cancer Prevention, University of Texas MD Anderson, Houston, TX, United States.
Department of General Internal Medicine and Pulmonary Medicine, University of Texas MD Anderson, Houston, TX, United States.
Front Oncol. 2020 Mar 24;10:276. doi: 10.3389/fonc.2020.00276. eCollection 2020.
The observation that cancer acquires significant changes in its metabolism dates back nearly a century, to Otto Warburg noting that cancer cells preferentially utilize glycolysis even when there are no hypoxic conditions in the growth media. Altered energetics are thus considered a hallmark of cancer. However, it has become clear that altered metabolism is not limited to cellular energetic pathways. Alterations in amino acid synthesis and catabolism, lipid biogenesis, and other pathways such as polyamine processing are commonly seen in cancer. Additionally, alterations in metabolism do not only have profound effects for cancer cells but also affect their surrounding microenvironment. With new cancer therapeutics targeting the immune microenvironment, these effects may have implications on cancer growth and response to therapy. These interactions are profound in lung cancer, further demonstrating the manifold interactions between developing tumors and the inflammatory microenvironment. Here, we discuss how dysregulation of metabolism in cancer alters its microenvironment and how this newfound knowledge can be exploited for anticancer treatment.
癌症在代谢方面出现显著变化这一观察结果可以追溯到近一个世纪前,当时奥托·瓦伯格注意到癌细胞即使在生长培养基中不存在缺氧条件时也优先利用糖酵解。因此,能量代谢改变被认为是癌症的一个标志。然而,现在已经清楚的是,代谢改变并不局限于细胞能量途径。氨基酸合成与分解代谢、脂质生物合成以及其他途径(如多胺加工)的改变在癌症中很常见。此外,代谢改变不仅对癌细胞有深远影响,还会影响其周围的微环境。随着针对免疫微环境的新型癌症治疗方法的出现,这些影响可能对癌症生长和治疗反应产生影响。这些相互作用在肺癌中非常显著,进一步证明了正在发展的肿瘤与炎症微环境之间的多种相互作用。在这里,我们讨论癌症中代谢失调如何改变其微环境,以及如何利用这一新发现的知识进行抗癌治疗。