Blum R, Kloog Y
Department of Pathology and Cancer Institute, Smilow Research Center, New York University School of Medicine, New York, NY, USA.
Department of Neurobiology, Tel Aviv University, Tel Aviv, Israel.
Cell Death Dis. 2014 Feb 20;5(2):e1065. doi: 10.1038/cddis.2014.38.
Pancreatic ductal adenocarcinoma, an aggressively invasive, treatment-resistant malignancy and the fourth leading cause of cancer deaths in the United States, is usually detectable only when already inevitably fatal. Despite advances in genetic screening, mapping and molecular characterization, its pathology remains largely elusive. Renewed research interest in longstanding doctrines of tumor metabolism has led to the emergence of aberrant signaling pathways as critical factors modulating central metabolic networks that fuel pancreatic tumors. Such pathways, including those of Ras signaling, glutamine-regulatory enzymes, lipid metabolism and autophagy, are directly affected by genetic mutations and extreme tumor microenvironments that typify pancreatic tumor cells. Elucidation of these metabolic networks can be expected to yield more potent therapies against this deadly disease.
胰腺导管腺癌是一种侵袭性强、对治疗耐药的恶性肿瘤,是美国癌症死亡的第四大主要原因,通常只有在已不可避免地致命时才能被检测到。尽管在基因筛查、图谱绘制和分子特征分析方面取得了进展,但其病理学在很大程度上仍然难以捉摸。对肿瘤代谢长期学说的重新研究兴趣导致异常信号通路的出现,这些通路是调节为胰腺肿瘤提供能量的中心代谢网络的关键因素。这些通路,包括Ras信号通路、谷氨酰胺调节酶、脂质代谢和自噬通路,直接受到典型胰腺肿瘤细胞的基因突变和极端肿瘤微环境的影响。预计对这些代谢网络的阐明将产生针对这种致命疾病的更有效疗法。