Enhancing Antitumor Immunity with PP4 Inhibition and Chemoimmunotherapy
Abstract
Current treatments are often able to initially control ovarian cancer growth. However, most of the time, ovarian cancer will grow back and will become resistant to therapy. Many cancer types have benefited from immunotherapy, which is an approach that stimulates the immune system to attack and kill the tumor cells while leaving normal cells untouched, just as it would a virus or bacteria that had infected the body. Unfortunately, this type of treatment has not worked well for women with ovarian cancer. The long-term goal of this proposed work is to develop new treatment strategies and discover new treatment targets for all American women with ovarian cancer in order to improve quality of life and survival. Recent studies have found that inhibitors of DNA damage repair can increase responses to immunotherapy, but there remains a gap in the understanding of which DNA repair targets may enhance anti-tumor drug activity. My previous work has shown that, by blocking the protein phosphatase 4 (PP4) complex, cancer cell death is enhanced after treatment with chemotherapy; but we currently do not know how PP4 inhibition may affect the anti-tumor effect of immunotherapy. Our hypothesis is that PP4 inhibition will promote tumor cell killing by the immune system that is enhanced when combined with immunotherapy. My proposal seeks to use a combination of human ovarian cancer cell lines, clinical ovarian cancer samples, and animal models to understand how targeting PP4 may enhance immunotherapy in advanced stage ovarian cancer. The rationale for the proposed research is that, once it is known how PP4 expression affects the response to immunotherapy, we can then use this information to develop novel inhibitors of PP4. Given the current prevalence of recurrent, chemoresistant disease in ovarian cancer, this work is anticipated to have an enormous impact for women battling ovarian cancer, who currently lack truly effective treatment options following disease recurrence. Ovarian cancer treatment is an uphill battle in crucial need of new approaches and treatment options. My career goal is to become an independent investigator in ovarian cancer research. The mentorship, collaborations, and working relationships I will develop while participating in the Ovarian Cancer Academy are vital to my development as an independent investigator and to the quality and success of my research. I am fully committed and look forward to participating in Academy-related activities and networking events, including webinars and bi-annual meetings. This award would provide me with the opportunity to build a strong translational research program and acquire the knowledge and data that will allow me to become a productive and innovative, independent scientist in ovarian cancer research.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110489
Entities
People
- Marion Curtis
Organizations
- Mayo Clinic Scottsdale
- United States Army