synthetic lethality
A therapeutic strategy where combined inhibition of two genes or pathways is lethal to cancer cells but tolerable to normal cells.
Full Definition
Synthetic lethality is a genetic interaction where the simultaneous disruption of two genes or pathways results in cell death, while disruption of either alone is survivable. In precision oncology, this concept is exploited therapeutically by targeting pathways that are essential for survival in cancer cells with specific genetic defects but dispensable in normal cells. The classic example involves PARP inhibitors in BRCA-deficient cancers, where cancer cells cannot repair DNA damage through either pathway. This approach expands the druggable genome beyond traditional oncogenes and tumor suppressors, creating therapeutic opportunities for cancers with loss-of-function mutations that are typically considered undruggable.
Usage
Usage note: Always provide mechanistic context when first introduced in clinical documents
In Context
- "PARP inhibitors exploit synthetic lethality in BRCA-mutated ovarian cancers." — Mechanism of action documentation
- "Identifying synthetic lethal partners of tumor suppressors represents a major therapeutic opportunity." — Drug discovery research proposal