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Acta Biochim Biophys Sin (Shanghai). 2016 Nov;48(11):969-979. Epub 2016 Sep 20.

Energy sources identify metabolic phenotypes in pancreatic cancer.

Liang C1,2,3, Qin Y1,2,3, Zhang B1,2,3, Ji S1,2,3, Shi S1,2,3, Xu W1,2,3, Liu J1,2,3, Xiang J1,2,3, Liang D1,2,3, Hu Q1,2,3, Liu L1,2,3, Liu C1,2,3, Luo G1,2,3, Ni Q1,2,3, Xu J4,2,3, Yu X4,2,3.

Author information

1
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
2
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
3
Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
4
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China yuxianjun@fudanpci.org xujin@fudanpci.org.

Abstract

Metabolic reprogramming is one of the emerging hallmarks of cancers. As a highly malignant tumor, pancreatic ductal adenocarcinoma (PDA) is not only a metabolic disease but also a heterogeneous disease. Heterogeneity induces PDA dependence on distinct nutritive substrates, thereby inducing different metabolic phenotypes. We stratified PDA into four phenotypes with distinct types of energy metabolism, including a Warburg phenotype, a reverse Warburg phenotype, a glutaminolysis phenotype, and a lipid-dependent phenotype. The four phenotypes possess distinct metabolic features and reprogram their metabolic pathways to adapt to stress. The metabolic type present in PDA should prompt differential imaging and serologic metabolite detection for diagnosis and prognosis. The targeting of an individual metabolic phenotype with corresponding metabolic inhibitors is considered a promising therapeutic approach and, in combination with chemotherapy, is expected to be a novel strategy for PDA treatment.

KEYWORDS:

Warburg effect; metabolic inhibitor; metabolic phenotype; pancreatic cancer; reverse Warburg effect

PMID:
27649892
DOI:
10.1093/abbs/gmw097
[Indexed for MEDLINE]

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