最早的代谢变化与胰腺癌的启动有关
Earliest Metabolic Changes Associated with the Initiation of Pancreatic Cancer
影响因子:16.60000
分区:医学1区 Top / 肿瘤学1区
发表日期:2024 Jul 15
作者:
Peter Storz
摘要
通常在肿瘤已经转移时在后期发现胰腺癌。因此，它的预后较差，5年生存率为11％至12％。瞄准这种高死亡率的关键是开发在胰腺局部局势的疾病中检测该疾病的方法。但是，这需要更好地了解控制胰腺癌肿瘤发生的事件。在本期癌症研究期间，Neuß及其同事报告了与腺泡到导直肠化生（ADM）相关的代谢变化，这是一个引发事件，导致形成胰腺导管腺癌（PDAC）的前体病变（PDAC）。他们的发现表明，转向有氧糖酵解，C-MYC信号增加并增加丝氨酸代谢作为ADM过程的驱动因素。这些发现很重要，因为它们证明了驱动全面PDAC的增殖和转移的代谢变化始于最早的病变。这些数据不仅提供了有关PDAC如何发展的见解，而且还提供了对先前描述的发现的潜在解释，例如即使不存在现场癌，也可以检测到循环病变细胞。总而言之，本文与我们对代谢重编程如何驱动最早导致PDAC开发的最早事件的理解高度相关，并可能为开发早期检测或干预的方法奠定基础。参见Neuß等人的相关文章，p。 2297。
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.