厌氧糖酵解
癌症研究
糖酵解
索拉非尼
丙酮酸激酶
肝细胞癌
巴基斯坦卢比
癌症
PI3K/AKT/mTOR通路
生物
医学
转移
癌细胞
内科学
信号转导
生物化学
新陈代谢
作者
Feng Jiao,Jingjing Li,Liwei Wu,Qiang Yu,Jie Ji,Jianye Wu,Weiqi Dai,Chuanyong Guo
标识
DOI:10.1186/s13046-020-01629-4
摘要
Abstract Liver cancer has become the sixth most diagnosed cancer and the fourth leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is responsible for up to 75–85% of primary liver cancers, and sorafenib is the first targeted drug for advanced HCC treatment. However, sorafenib resistance is common because of the resultant enhancement of aerobic glycolysis and other molecular mechanisms. Aerobic glycolysis was firstly found in HCC, acts as a hallmark of liver cancer and is responsible for the regulation of proliferation, immune evasion, invasion, metastasis, angiogenesis, and drug resistance in HCC. The three rate-limiting enzymes in the glycolytic pathway, including hexokinase 2 (HK2), phosphofructokinase 1 (PFK1), and pyruvate kinases type M2 (PKM2) play an important role in the regulation of aerobic glycolysis in HCC and can be regulated by many mechanisms, such as the AMPK, PI3K/Akt pathway, HIF-1α, c-Myc and noncoding RNAs. Because of the importance of aerobic glycolysis in the progression of HCC, targeting key factors in its pathway such as the inhibition of HK2, PFK or PKM2, represent potential new therapeutic approaches for the treatment of HCC.
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