Roles of the PI3K/Akt pathway in Epstein-Barr virusinduced cancers and therapeutic implications

• 作者: Jiezhong Chen
• 来源期刊: 世界病毒学杂志
• 学科: 医学
• 关键词: EPSTEIN-BARR virus LATENT MEMBRANE PROTEINS 1 LATENT MEMBRANE PROTEINS 2A PHOSPHOINOSITIDE 3-kinase/protein KINASE B Carcinogenesis Drug resistance
• 年，卷（期）: 2012,（6）
• 页码范围: 154-161
• 页数: 8页
• 分类号: R

摘要

Viruses have been shown to be responsible for 10%-15%of cancer cases.Epstein-Barr virus(EBV)is the first virus to be associated with human malignancies.EBV can cause many cancers,including Burkett’s lymphoma,Hodgkin’s lymphoma,post-transplant lymphoproliferative disorders,nasopharyngeal carcinoma and gastric cancer.Evidence shows that phosphoinositide 3-kinase/protein kinase B(PI3K/Akt)plays a key role in EBV-induced malignancies.The main EBV oncoproteins latent membrane proteins(LMP)1 and LMP2A can activate the PI3K/Akt pathway,which,in turn,affects cell survival,apoptosis,proliferation and genomic instability via its downstream target proteins to cause cancer.It has also been demonstrated that the activation of the PI3K/Akt pathway can result in drug resistance to chemotherapy.Thus,the inhibition of this pathway can increase the therapeutic efficacy of EBV-associated cancers.For example,PI3K inhibitor Ly294002 has been shown to increase the effect of 5-fluorouracil in an EBV-associated gastric cancer cell line.At present,dual inhibitors of PI3K and its downstream target mammalian target of rapamycin have been used in clinical trials and may be included in treatment regimens for EBV-associated cancers.