Subproject for Dr. Mirkin

Treating cancer has been a daunting task. Ovarian cancer in particular has not seen a real improvement in treatment outcome in 30 years. The standard approach to developing new drugs for cancer treatment is to target genes that drive cancer growth and survival. However, tumors seem to always contain cancer cells that are independent of the targeted protein and hence grow out. One possible tool for cancer therapy could be the death receptor, Fas and its ligand FasL. Stimulation of Fas instructs cancer cells to commit suicide. We recently realized that not the stimulation of Fas but surprisingly its elimination causes all cancer cells to die without affecting normal cells. We believe that this is due to the function of Fas as a target for immune cells to specifically kill cancer cells. We now hypothesize that whenever a cancer cell is generated that loses Fas or its ligand FasL it dies as a fail safe mechanism. We propose to exploit this mechanism and generate new spherical nucleic acid (SNA)-based agents that selectively eliminate FasL from cancer cells. We will treat ovarian cancer mouse models with these new constructs with the goal of bringing this treatment to the clinic to treat of ovarian cancer patients.