We target next generation synthetic lethal therapeutics within precision oncology, focusing on genetically-defined patient populations.

The first generation of approved targeted therapies were predominately directed at driver mutations, which target specific types of receptor tyrosine kinases, such as BCR-ABL, EGFR and HER2. Since then, a rapid evolution in the understanding of tumor biology coupled with an improved ability to segment subsets of tumors based on genomic alterations have led to the development of new generations of targeted cancer therapies for a variety of additional tumor-specific genomic abnormalities.

Targeting DNA repair genes and specifically loss-of-function alterations is an emerging area of research in precision oncology, with PARP inhibitors pioneering the field. Synthetic lethality (SL) represents a clinically-validated approach to drug development that also targets genomic instability lesions caused by mutations in mechanisms that govern DNA damage repair.

SL arises when a deficiency in either of two genes is tolerated in cells, but simultaneous deficiencies in both genes cause cell death. Cancer cells that contain an inactivating mutation in one gene of a SL pair are susceptible to therapeutic intervention targeting the other gene pair.