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2021-06-17
Synthetic Lethality
Genomic instability is one of the hallmarks of cancer cells, and the resultant mutations render cancer cells more dependent on alternative pathways for survival and proliferation, so these cancer cells are more vulnerable to targeted perturbations on those alternative pathways – a phenomenon known as synthetic lethality.
Synthetic lethality is an especially attractive and effective approach to targeting some common oncogenes that have been traditionally considered as undruggable. Synthetic lethality also has the potential to overcome the therapeutic resistance caused by new mutations that often occur with the treatment of conventional targeted therapies. Furthermore, therapies addressing synthetic lethality targets can have anti-tumor effects that are complementary to or synergistic with therapeutics employing other mechanisms. Synthetic lethality can be exploited as a drug development approach to selectively target cancer cells with certain mutations, for example, deficiencies in DNA damage response (DDR), and we see this approach usher in a new paradigm for targeted anti-cancer therapy.
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