胰腺癌通常在晚期才被发现，此时肿瘤已经发生转移；因此，其预后较差，5年生存率为11%～12%。针对这种高死亡率的关键是开发在疾病仍局限于胰腺的阶段检测该疾病的方法。然而，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》中，Neuß 及其同事报告了与腺泡导管化生 (ADM) 相关的代谢变化，这是一种导致胰腺导管腺癌 (PDAC) 前驱病变形成的起始事件。他们的研究结果表明，有氧糖酵解的转变、c-MYC 信号传导的增加和丝氨酸代谢的增加是 ADM 过程的驱动因素。这些发现很重要，因为它们表明，驱动成熟 PDAC 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对 PDAC 如何发展的见解，还为之前描述的发现提供了潜在的解释，例如即使不存在原位癌，也可以检测到循环病变细胞。总之，本文对于进一步了解代谢重编程如何驱动导致 PDAC 发展的最早事件具有重要意义，并可以为开发早期检测或干预方法奠定基础。请参阅 Neuß 等人的相关文章，第 17 页。 2297.©2024 美国癌症研究协会。

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.©2024 American Association for Cancer Research.