与胰腺癌发生相关的最早代谢变化

Earliest Metabolic Changes Associated with the Initiation of Pancreatic Cancer

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CANCER RESEARCH

影响因子:16.6

分区:医学1区 Top / 肿瘤学1区

发表日期:2024 Jul 15

作者: Peter Storz

DOI: 10.1158/0008-5472.CAN-24-0874

摘要

胰腺癌通常在晚期被发现，此时肿瘤已发生转移，因此其预后极差，5年生存率仅为11%至12%。针对这一高死亡率的关键是开发在肿瘤仍局限于胰腺时即可检测的方法。然而，这需要更深入理解胰腺癌发生的机制。在《癌症研究》本期中，Neuß及其同事报道了与腺泡-导管转化（ADM）相关的代谢变化，ADM是导致胰腺导管腺癌（PDAC）前驱病变形成的启动事件。他们的研究发现，ADM过程中存在向有氧糖酵解的切换、c-MYC信号增强以及丝氨酸代谢增加，这些都被认为是驱动因素。这些发现表明，驱动PDAC增殖和转移的代谢变化始于最早期的病变。这些数据不仅提供了PDAC发展的新见解，还可能解释先前发现的现象，例如即使没有原位癌，循环中的病变细胞也可以被检测到。总之，这篇文章对理解代谢重编程如何驱动PDAC的早期事件具有重要意义，并可能为早期检测或干预方法的开发奠定基础。相关论文请参见Neuß等人，第2297页。

Abstract

Pancreatic cancer is usually detected at a late stage, when tumors have already metastasized; therefore, it has a poor prognosis with a 5-year survival rate of 11% to 12%. A key to targeting this high mortality is to develop methods for detecting the disease at a stage in which it is still local to the pancreas. However, this needs a better understanding of the events that govern pancreatic cancer oncogenesis. In this issue of Cancer Research, Neuß and colleagues report metabolic changes associated with acinar-to-ductal metaplasia (ADM), an initiating event that leads to the formation of precursor lesions for pancreatic ductal adenocarcinoma (PDAC). Their findings reveal a switch to aerobic glycolysis, increased c-MYC signaling, and increased serine metabolism as driving factors for the ADM process. These findings are important as they demonstrate that metabolic changes that drive the proliferation and metastasis of full-blown PDAC begin in the earliest lesions. The data not only provide insights into how PDAC develops but also a potential explanation for previously described findings, such as circulating lesion cells can be detected even when no carcinoma in situ is present. In summary, this article is highly relevant for furthering our understanding of how metabolic reprogramming drives the earliest events leading to PDAC development and could lay the groundwork for developing methods for early detection or intervention. See related article by Neuß et al., p. 2297.