Synthetic Lethality
Therapeutic strategy where drugs target pathways that become essential for survival when cancer cells have specific genetic defects.
Full Definition
Synthetic lethality occurs when the simultaneous loss of function of two genes or pathways results in cell death, while loss of either alone is tolerable. In cancer therapy, this concept is exploited by using drugs to target pathways that become essential when cancer cells harbor specific mutations or deletions. The classic example is PARP inhibitor therapy in BRCA-deficient tumors, where DNA repair defects make cells dependent on alternative repair mechanisms. This approach allows selective targeting of cancer cells while sparing normal cells that retain functional repair pathways. Synthetic lethal interactions are increasingly being identified through genetic screens and computational approaches, offering new therapeutic opportunities for cancers with specific molecular vulnerabilities.
In Context
- "The synthetic lethality approach using PARP inhibitors showed remarkable efficacy in BRCA1-mutated ovarian cancer." — Clinical trial report
- "Computational screening identified novel synthetic lethal partnerships for RAS-driven cancers." — Research methodology