Fig. 1. Scenarios for targeting metabolic enzymes that produce essential cellular building blocks in cancer.

a Targeting a metabolic enzyme to disrupt the production of a metabolite that is essential to a cancer cell can be an effective therapeutic strategy. b When there are alternate means for production or acquisition of an essential metabolite, targeting the synthesizing enzyme may be inadequate to kill a cancer cell. c An alternative approach is to target an enzyme directly downstream of a toxic metabolite, which will result in accumulation of the upstream toxic metabolite. Even if there are alternative routes for producing the building block metabolite, this strategy should still work to exert toxicity in a cancer cell.