Proposed mechanism for Ets-1 mediated drug resistance in ovarian cancer. A) In the absence of abundant Ets-1 expression, the transsulfuration pathway is the main cysteine source for glutathione synthesis. Treatment with chemotherapeutic agents induces oxidative stress that causes DNA damage and GSH depletion by increasing intracellular ROS, leading to cell death. B) Under the control of Ets-1 expression, Sxc- activity is increased to bolster cysteine stores thereby increasing intracellular glutathione. High levels of glutathione prevent oxidative stress-inducing therapies from causing an accumulation of ROS. Thus, Ets-1 overexpression may play an important role in the drug resistance often observed in aggressive ovarian cancer.