Synthetic Lethality
Synthetic Lethality (SL) is a significant biological phenomenon in which the simultaneous loss of function—such as through gene mutation, silencing, or pharmacological inhibition—of two otherwise non-lethal genes (or associated pathways) results in cell death.
Mechanism Explained: The Cellular "Fail-Safe" System
To maintain essential life processes, such as DNA repair and metabolic regulation, cells often employ multiple backup pathways. If the function of one gene (e.g., Gene A) is lost, another gene (e.g., Gene B) can compensate, allowing the cell to survive. However, when both genes fail simultaneously, the cell loses all backup support and undergoes death.
Application in Cancer Therapy
Many cancer cells carry specific gene mutations (e.g., in BRCA1/2), making them reliant on alternative pathways for survival. By using targeted drugs (such as PARP inhibitors) to inhibit these backup pathways, selective killing of cancer cells can be achieved. Normal cells, which retain intact pathways, remain unaffected. As research advances, synthetic lethality strategies are being expanded to more cancer types, establishing this approach as a key pillar of precision medicine.
