Targeting CIP2A for the Potential Treatment of Ovarian Cancer
Abstract
The National Cancer Institute predicts over 21,000 new ovarian cancer cases and over 13,500 ovarian cancer-related deaths will occur in the U.S. in 2021. While early detection of ovarian cancer improves survival, a majority of ovarian cancers are detected at later stages. While therapies are available to treat ovarian cancer patients, including targeted and platinum-based chemotherapies, severe side effects and the development of resistance remain major limitations of current treatments. In high-grade ovarian cancer, 15-25% of patients experience primary treatment resistance, and a majority of those who relapse in the first year develop resistance to platinum therapies. In addition, while the 5-year survival rate for ovarian cancer has been improving, as of 2017 the rate was still below 50%. Thus, there is a need to develop new therapies to improve outcomes and care for patients with ovarian cancer, particularly for cancers that have developed resistance to chemotherapies. The oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) is overexpressed in over 65% of human ovarian cancer cases, and its overexpression is associated with poor prognosis in the most common form of ovarian cancer. Decreasing the levels of this oncoprotein has been shown to decrease ovarian cancer cell proliferation and increase sensitivity to platinum-based therapy. Thus, targeting CIP2A may be a promising approach to overcome resistance to platinum-based therapies and improve treatment of ovarian cancer. This would benefit Service Members, Veterans, their family members, and other women who suffer from ovarian cancer. The proposed research will explore two different types of novel peptides to decrease the expression of CIP2A and the growth and viability of ovarian cancer cells. Upon completion of the proposed research, we expect to have identified promising compounds that decrease ovarian cancer cell growth by decreasing CIP2A and that improve sensitivity to platinum-based treatments. This research will provide proof of concept for a fundamentally new approach to treating cancer and overcoming drug resistance that could ultimately lead to a breakthrough in ovarian cancer treatment.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210268
Entities
People
- J Aldrich
Organizations
- United States Army
- University of Florida