Genome sequencing has opened up the door for oncologists and researchers to utilize synthetic lethality, a technique that exploits cancer-specific genetic deficits to identify targets that are paramount to cancer cell viability. Their research is published online in the Proceedings of the National Academy of Sciences (PNAS). Scientists at the San Diego branch of Ludwig Institute for Cancer Research and the University of California San Diego School of Medicine demonstrated that inhibiting a key enzyme led to both breast and ovarian cancer cells to die and in mouse studies reduced tumor growth.
Lead researcher Richard D. Kolodner, PhD, Distinguished Professor of Medicine and Cellular and Molecular Medicine, investigated Saccharomyces cerevisiae, a species of yeast used in basic research, to search for synthetic lethal relationships. Their focus was Flap Endonuclease 1 (FEN1), a DNA structure-specific endonuclease involved in DNA replication and repair. Researchers found that when they blocked functions of FEN1 using a small molecule inhibitor or genetic ablation, BRCA1 and BRCA2 mutant cancer cell lines were targeted and killed. Normal cells were able to recover from FEN1 inhibition.