Zhang Jinyi, Kong Xueqing, Zhou Boyan, Li Rui, Yu Zhaoan, Zhu Jinrong, Xi Qing, Li Yan, Zhao Zichao, Zhang Rongxin
Guangdong Provincial Key Laboratory for Biotechnology Drug Candidates, Department of Biotechnology, Laboratory of Immunology and Inflammation, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou,The Second Clinical Medical School of Guangdong Pharmaceutical University, Guangzhou, China
Department of Emergency Medicine, Shaodong People's Hospital, Shaodong City, Hunan Province, China
Mol Aspects Med. 2025 Jun;103:101368. doi: 10.1016/j.mam.2025.101368. Epub 2025 May 20.
Pancreatic cancer is a highly aggressive gastrointestinal malignancy, often termed the "king of cancers" due to its notoriously high mortality rate. Its clinical characteristics, including late diagnosis, low surgical resectability, high recurrence rates, significant chemoresistance, and poor prognosis have collectively driven the persistent rise in incidence and mortality. Despite ongoing advancements in therapeutic strategies, the management of pancreatic cancer, particularly at advanced stages, remains challenging. Chemotherapy remains the mainstay of current treatment. However, the prevalent problem of chemotherapy resistance poses a significant obstacle to effective treatment. Metabolic reprogramming, characterized by alterations in glucose metabolism, lipid biosynthesis, and amino acid utilization, supports the high energy demands and rapid proliferation of cancer cells. Emerging evidence suggests that these metabolic changes, possibly mediated by epigenetic mechanisms, also contribute to tumorigenesis and metastasis. These findings highlight the critical role of metabolic alterations in pancreatic cancer pathogenesis. This review explores the relationship between metabolic reprogramming and chemotherapy resistance, discussing underlying mechanisms and summarizing preclinical studies and drug development targeting metabolism. The aim is to provide a comprehensive perspective on potential therapeutic strategies for pancreatic cancer.
胰腺癌是一种侵袭性很强的胃肠道恶性肿瘤，因其极高的死亡率常被称为“癌中之王”。其临床特征包括诊断晚、手术可切除性低、复发率高、显著的化疗耐药性以及预后差，这些因素共同导致了发病率和死亡率的持续上升。尽管治疗策略不断进步，但胰腺癌的治疗，尤其是晚期胰腺癌的治疗，仍然具有挑战性。化疗仍然是当前治疗的主要手段。然而，普遍存在的化疗耐药问题对有效治疗构成了重大障碍。代谢重编程以葡萄糖代谢、脂质生物合成和氨基酸利用的改变为特征，支持癌细胞对高能量的需求和快速增殖。新出现的证据表明，这些代谢变化可能由表观遗传机制介导，也有助于肿瘤的发生和转移。这些发现突出了代谢改变在胰腺癌发病机制中的关键作用。本综述探讨了代谢重编程与化疗耐药之间的关系，讨论了潜在机制，并总结了针对代谢的临床前研究和药物开发。目的是为胰腺癌的潜在治疗策略提供一个全面的视角。
