Synthetic lethality: exploiting the addiction of cancer to DNA repair

摘要: Because cancer at its origin must acquire permanent genomic mutations, it is by definition a disease of DNA repair. Yet for cells to replicate their and divide, which the fundamental phenotype cancer, multiple repair pathways are required. This produces paradox cell, where same time weakness. To overcome this difficulty, cell often becomes addicted other than one that led initial mutability. The best example in breast or ovarian cancers with mutated BRCA1 2, essential components pathway repairing double-strand breaks. replicating requires breaks, these have become reliant on another component, PARP1, replication fork progression. inhibition PARP1 results catastrophic breaks during replication, ultimately death. exploitation addiction based synthetic lethality has wide applicability treatment many types malignancies, including those hematologic origin. There large number novel compounds clinical trials use mechanism antineoplastic activity, making most important new concepts recent drug development.