Figure 1.

(a) Structure of CF10 with PEG6 (blue) and AraC (yellow) modifications. (b) Differential metabolism of CF10 and 5-FU resulting in increased DNA damage with CF10 treatment and vulnerability to inhibitors of DNA repair. (c) Activation of the intra-S-phase checkpoint thru the ATR/Chk1 pathway and phosphorylation of Wee1. Our studies showed that inhibition of ATR or Wee1 enhances cytotoxicity of CF10, but not 5-FU, to PDAC cells. The combination of CF10+ATRi/Wee1 inhibition may overcome 5-FU resistance for improved treatment of PDAC.