Synthetic lethality (합성치사) arises when a combination of mutations in two or more genes leads to cell death, whereas a mutation in only one of these genes does not, and by itself is said to be viable. (http://en.wikipedia.org/wiki/Synthetic_lethality)
하나의 유전자 고장으로는 죽지 않지만, 두개 이상이 동시에 고장일 경우 세포가 죽는 현상을 합성치사(synthetic lethality)라고 하는데, 암(Cancer)세포는 이미 특정 유전자가 고장이므로, 조합으로 고장시 세포가 죽게 될 유전자를 찾아 그 유전자를 타겟으로 하는 약물을 만들면 암세포만 선택적으로 죽일 수 있다. DrugBank 데이터베이스를 참고하면, 특정 유전자를 타겟으로 하는 FDA승인 약물과 연구중 약물을 알 수 있다.
사례
- (BRCA1 or BRCA2) vs. PARP --> PARP inhibitor
- (BRCA1 or BRCA2) vs. RAD52
- ARID1A vs. EZH2 --> Kinase inhibitor (Dasatinib)
관련 논문
- Synthetic lethal therapies for cancer: what’s next after PARP inhibitors? Nature Reviews Clinical Oncology
- Synthetic lethality and cancer Nature Reviews Genetics
- DAISY: picking synthetic lethals from cancer genomes Cancer Cell
- Predicting cancer-specific vulnerability via data-driven detection of synthetic lethality Cell
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