Project 466529

Ovarian cancer is a deadly disease with limited options for treatment. Typical treatment for ovarian cancer consists of a combination of surgery and chemotherapy with cisplatin (CDDP). While this initial treatment usually results in remission, the cancer often returns, resistant to CDDP. Therefore, novel therapies are needed in these cases. A relatively novel avenue for cancer therapy involves inducing the process of immunogenic cell death (ICD). ICD is a type of cell death that involves the release of danger signals. These danger signals can then act as a vaccine to stimulate the immune system to attack the cancer cells of origin and prevent recurrence of the cancer after its initial remission. While CDDP is toxic to cancer cells, it is incapable of inducing ICD. CDDP kills cancer cells through a traditional cell death mechanism that does not result in the release of danger signals. Therefore, it is possible that combining CDDP with other drugs that are capable of generating ICD could increase CDDP's toxicity to cancer cells and prevent the recurrence of the cancer. Two candidate drugs that could act as ICD inducers are mifepristone and nelfinavir. Both of these drugs have demonstrated the ability to kill ovarian cancer cells, as well as activate some of the cellular pathways that are required for ICD. Therefore, the goal of this project will be to determine if these drugs are capable of inducing ICD, and to determine whether these drugs increase the toxicity of CDDP when used in combination.