synthetic lethality

Synthetic lethality is a strategy that kills cancer cells by exploiting a weakness they already carry. The idea rests on backup systems: some cellular jobs have two independent routes, so a cell can lose one and survive on the other. If a tumor has already lost one route through mutation, a drug that knocks out the surviving backup will kill it — while a healthy cell, which still has both routes, shrugs off the same drug.

The classic case involves DNA repair. Some cancers, especially certain breast and ovarian tumors, carry a broken copy of a gene needed for one DNA-repair pathway and lean entirely on a second pathway to survive. A drug that blocks an enzyme central to that second pathway leaves the cancer cell with no way to fix its DNA, so its damage piles up and it dies. Normal cells, retaining the first pathway, are largely spared.

Synthetic lethality is powerful because the selectivity comes from the tumor's own genetics rather than from a tumor-specific target, opening a way to attack cancers driven by lost gene functions that are otherwise hard to drug. The catch is that it only works in patients whose tumor carries the right pre-existing defect, and tumors can develop resistance by restoring the lost pathway.