Targeting the PI3K/Akt/mTOR Pathway in Hepatocellular Carcinoma

被引：222

作者：

Sun, Eun Jin ^{[1
,2
]}

Wankell, Miriam ^{[1
]}

Palamuthusingam, Pranavan ^{[3
,4
]}

McFarlane, Craig ^{[1
]}

Hebbard, Lionel ^{[1
,5
,6
]}

机构：

[1] James Cook Univ, Coll Publ Hlth Med & Vet Sci, Australian Inst Trop Med & Hlth, Ctr Mol Therapeut,Dept Mol & Cell Biol, Townsville, Qld 4811, Australia

[2] James Cook Univ, Coll Med & Dent, Townsville, Qld 4811, Australia

[3] Townsville Univ Hosp, Inst Surg, Townsville, Qld 4811, Australia

[4] Mater Hosp, Townsville, Qld 4811, Australia

[5] Westmead Hosp, Westmead Inst Med Res, Storr Liver Ctr, Sydney, NSW 2145, Australia

[6] Univ Sydney, Sydney, NSW 2145, Australia

来源：

BIOMEDICINES | 2021年 / 9卷 / 11期

关键词：

hepatocellular carcinoma; HCC; Akt; mTOR; PI3K; clinical trials; NF-KAPPA-B; ELEMENT-BINDING PROTEIN; GLYCOGEN-SYNTHASE KINASE-3; FATTY LIVER-DISEASE; PHASE-II TRIAL; PROMOTES TUMORIGENESIS; 1ST-LINE TREATMENT; TUMOR-SUPPRESSOR; COMPLEX ROLES; PIVOTAL ROLE;

D O I：

10.3390/biomedicines9111639

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Despite advances in the treatment of cancers through surgical procedures and new pharmaceuticals, the treatment of hepatocellular carcinoma (HCC) remains challenging as reflected by low survival rates. The PI3K/Akt/mTOR pathway is an important signaling mechanism that regulates the cell cycle, proliferation, apoptosis, and metabolism. Importantly, deregulation of the PI3K/Akt/mTOR pathway leading to activation is common in HCC and is hence the subject of intense investigation and the focus of current therapeutics. In this review article, we consider the role of this pathway in the pathogenesis of HCC, focusing on its downstream effectors such as glycogen synthase kinase-3 (GSK-3), cAMP-response element-binding protein (CREB), forkhead box O protein (FOXO), murine double minute 2 (MDM2), p53, and nuclear factor-kappa B (NF-kappa B), and the cellular processes of lipogenesis and autophagy. In addition, we provide an update on the current ongoing clinical development of agents targeting this pathway for HCC treatments.

引用

页数：20

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