Blocking LPA-dependent signaling increases ovarian cancer cell death in response to chemotherapy

Proliferative signaling occurs inside a window that allows signaling molecules to be reversibly oxidized and reduced. Chemotherapeutic drugs push cells toward a higher oxidation state, which is necessary for effective cancer cell death. The side effect is oxidative damage to normal cells. Antioxidants have a broad range of effects on the oxidative state of normal and cancer cells. While antioxidants may help prevent oxidative damage to normal cells, the effect of the shift in redox state of a given tumor on the efficacy of chemotherapy treatment is variable. Ovarian cancer cells often make and/or respond to increased amounts of LPA, a growth factor found at high levels in ascites fluid. This sustained growth factor-dependent signaling increases cellular survival mechanisms preventing oxidative damage and promoting uncontrolled proliferation. Removing these signals dampens the peak of the survival curve allowing chemotherapeutics to more effectively kill the cancer cells and spare normal tissues.140