Combination therapy with BPTES nanoparticles and metformin targets the metabolic heterogeneity of pancreatic cancer

Amira Elgogary(Johns Hopkins University), Qingguo Xu(Johns Hopkins University), Brad Poore(Johns Hopkins University), Jesse Alt(Johns Hopkins University), Sarah C. Zimmermann(Johns Hopkins University), Liang Zhao(Johns Hopkins University), Jie Fu(Johns Hopkins University), Baiwei Chen(Johns Hopkins University), Shiyu Xia(Johns Hopkins University), Yanfei Liu(Johns Hopkins University), Marc Neisser(Johns Hopkins University), Christopher Nguyen(Johns Hopkins University), Ramon Lee(Johns Hopkins University), Joshua K. Park(Johns Hopkins University), Juvenal Reyes(Johns Hopkins University), Thomas Härtung(Johns Hopkins University), Camilo Rojas(Johns Hopkins University), Rana Rais(Johns Hopkins University), Takashi Tsukamoto(Johns Hopkins University), Gregg L. Semenza(Johns Hopkins University), Justin Hanes(Johns Hopkins University), Barbara S. Slusher(Johns Hopkins University), Anne Le(Johns Hopkins University)
Proceedings of the National Academy of Sciences
August 24, 2016
10.1073/pnas.1611406113
Cited by 230Open Access
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Abstract

Significance There are no effective therapies currently available for advanced pancreatic cancer. We show that there are two populations of cancer cells within a pancreatic tumor that require targeting by different metabolic inhibitors for effective tumor control. Rapidly dividing cells use glutamine, and can be effectively killed by administration of a nanoparticle containing an inhibitor of glutamine metabolism. Hypoxic cells, which are slowly dividing cells, metabolize glucose and can be targeted by metformin, a drug used for the treatment of diabetes. Clinical trials are needed to determine whether combination therapy, with drugs that effectively block the metabolism of glutamine and glucose, improves the survival of patients with pancreatic cancer.

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