1. Volume 32, Issue 1, Pages 3-5 (July 2017)
MUC-king with HIF May Rewire Pyrimidine Biosynthesis and Curb Gemcitabine Resistance in Pancreatic Cancer 
Chi V. Dang 
Cancer Cell 
Volume 32, Issue 1, Pages 3-5 (July 2017)
DOI: /j.ccell
Copyright © 2017 Elsevier Inc. Terms and Conditions

2. Figure 1
Diagram Illustrating the Transport of Glutamine, Glucose, and Gemcitabine into a PDAC Cell and the Subsequent Metabolism of These Substrates
Glucose and glutamine are shown to contribute to the production of phosphoribosyl pyrophosphate (PRPP) and, via the tricarboxylic acid (TCA) cycle, aspartate that with glutamine builds on the PRPP scaffold to produce dCTP for DNA replication. Gemcitabine or 2,2-difluoro 2-deoxycytidine (dFdC) is shown metabolized to difluorodeoxycytidine triphosphate (dFCTP), which competes with dCTP, incorporates into DNA, and causes damage. HIF is depicted to stimulate the non-oxidative pentose phosphate pathway (non-ox PPP) to produce PRPP as well as stimulate selected enzymes involved in pyrimidine synthesis. Because HIF largely influences glucose metabolism, it remains open as to whether MYC, which portends poor prognosis in PDAC, could participate in resistance with its known role to directly activate many genes involved in de novo pyrimidine synthesis. Digoxin, which inhibits the expression of HIF, and leflunomide, which inhibits dihydroorotate dehydrogenase (DHODH)—an enzyme involved in de novo pyrimidine synthesis—are shown.
Cancer Cell  , 3-5DOI: ( /j.ccell )
Copyright © 2017 Elsevier Inc. Terms and Conditions