TYMS and cancer: 5-FU resistance can result from multiple causes; however, a critical review of the literature indicates cancer cells adapt to 5-FU’s cytotoxic effects through: (1) decreasing intracellular FdUMP levels [Figure 1]; (2) elevating activity of the target enzyme, TS; and (3) dysregulating the balance between autophagy and apoptosis to favor cell survival.