期刊
CURRENT MEDICINAL CHEMISTRY
卷 24, 期 13, 页码 1321-1331出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867324666170206142658
关键词
PI3K-AKT pathway; mTOR inhibitor; pancreatic cancer; resistance; PDAC; biomarkers
资金
- Mashhad University of Medical Sciences
The phosphoinositide 3 kinase AKT mammalian target of rapamycin (PI3K-AKT-mTOR) signaling pathway is an important in the aetiology of pancreatic cancer (PC) and is frequently activated in PC. It is then associated with a poorer prognosis. Aberrant activation of this pathway is involved in cell metabolism and survival, cell cycle progression, regulation of apoptosis, protein synthesis, and genomic instability. Several agents have been developed to target the Akt/PI3K pathways, including PI3K inhibitors, (e.g. LY294002, Wortmannin), PI3K/mTOR inhibitors (e.g. BEZ235), or Akt inhibitors (e.g. perifosine, MK2206), which have been tested alone or in combinations with DNA-targeted agents (e.g., gemcitabine and fluorouracil) in pancreatic ductal adenocarcinoma (PDAC). However, due to their unfavorable pharmaceutical activities, toxicity, and crossover inhibition of other lipid and protein kinases, these compounds have not been used in clinical studies. In this review, we focus on the progress in the development of Akt, PI3K and mTOR inhibitors for clinical applications, together with the need for the development of in PDAC and the need for the identification of predictive biomarkers and combination strategies with less toxicity in counteracting the mechanisms of resistance to the therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据