Queen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute of Cell and Molecular Science, Centre for Diabetes, Inositide Signalling Group, London, UK.
Anticancer Agents Med Chem. 2011 Jun;11(5):455-63. doi: 10.2174/187152011795677382.
Pancreatic cancer has one of the poorest prognoses among all cancers partly because of its silent nature and tendency for late discovery but also because of its persistent resistance to chemotherapy. At present there are very limited treatment alternatives for pancreatic cancer, hence the need to develop novel and more efficient drugs. It is well known that mutations in K-Ras oncogene accumulate early in the disease progression and occur in almost all of pancreatic ductal adenocarcinomas (PDAC). A key downstream target of the Ras family is phosphoinositide 3-kinase (PI3K), the enzyme responsible for generation of 3-phosphorylated phosphoinositides and activation of Akt (Protein Kinase B/Akt). The PI3K/Akt pathway is involved in inhibition of apoptosis and stimulation of cell proliferation and it is has been estimated that at least 50% of all cancer types are related to deregulation of this signalling pathway. In this review we will discuss how the PI3K/Akt/mTOR signaling network is altered in pancreatic cancer and further give an overview of preclinical and clinical studies where this pathway has been targeted.
胰腺癌的预后在所有癌症中最差的原因之一是它的隐匿性和晚期发现的倾向，但也因为其对化疗的持续耐药性。目前，胰腺癌的治疗选择非常有限，因此需要开发新型、更有效的药物。众所周知，K-Ras 癌基因的突变在疾病进展的早期就会积累，并且几乎存在于所有胰腺导管腺癌（PDAC）中。 Ras 家族的一个关键下游靶标是磷酸肌醇 3-激酶（PI3K），它是负责生成 3-磷酸化磷酸肌醇和激活 Akt（蛋白激酶 B/Akt）的酶。PI3K/Akt 通路参与抑制细胞凋亡和刺激细胞增殖，据估计，至少有 50%的癌症类型与这种信号通路的失调有关。在这篇综述中，我们将讨论 PI3K/Akt/mTOR 信号网络在胰腺癌中是如何改变的，并进一步概述该通路已被靶向的临床前和临床研究。
