Synthetic Lethality

Inhibiting pathways that contribute to aberrant DNA repair and cellular metabolism

Accumulation of DNA damage, genomic instability, and altered cellular metabolism are pervasive characteristics of human tumors.1-3 Disruption of essential DNA damage repair or cellular metabolism in cancer cells may increase dependency on alternate repair pathways for cell survival or make tumors more susceptible to modulation of metabolic enzymes.2,4 Synthetically lethal therapies aim to combine pharmacologic inhibition of targeted pathways with tumor-inherent defects in key cellular processes that promote aberrant proliferation to selectively kill tumor cells while sparing healthy tissue.2,4-6 GSK is investigating a clinical asset that utilizes the power of synthetically lethal interactions to fight malignant cells in a variety of cancers.7