Francipane Maria Giovanna, Lagasse Eric
McGowan Institute for Regenerative Medicine, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Oncotarget. 2014 Jan 15;5(1):49-66. doi: 10.18632/oncotarget.1548.
The mammalian target of rapamycin (mTOR) has emerged as a potential target for drug development, particularly due to the fact that it plays such a crucial role in cancer biology. In addition, next-generation mTOR inhibitors have become available, marking an exciting new phase in mTOR-based therapy. However, the verdict on their therapeutic effectiveness remains unclear. Here we review phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling as one of the primary mechanisms for sustaining tumor outgrowth and metastasis, recent advances in the development of mTOR inhibitors, and current studies addressing mTOR activation/inhibition in colorectal cancer (CRC). We will also discuss our recent comparative study of different mTOR inhibitors in a population of colon cancer stem cells (CSCs), and current major challenges for achieving individualized drug therapy using kinase inhibitors.
雷帕霉素的哺乳动物靶点(mTOR)已成为药物开发的一个潜在靶点,特别是因为它在癌症生物学中起着至关重要的作用。此外,新一代mTOR抑制剂已经问世,标志着基于mTOR的治疗进入了一个令人兴奋的新阶段。然而,关于它们治疗效果的定论仍不明确。在这里,我们综述磷脂酰肌醇-3-激酶(PI3K)/Akt/mTOR信号传导作为维持肿瘤生长和转移的主要机制之一、mTOR抑制剂开发的最新进展,以及目前针对结直肠癌(CRC)中mTOR激活/抑制的研究。我们还将讨论我们最近在一群结肠癌干细胞(CSC)中对不同mTOR抑制剂的比较研究,以及使用激酶抑制剂实现个体化药物治疗目前面临的主要挑战。