Multimodal Theragnostic Anticancer Complexes of Rhenium to Circumvent Platinum Resistance in Relapsed Ovarian Cancer
Abstract
Rationale and Objective: The conventional platinum-based chemotherapeutic agents, cisplatin and carboplatin, are effective in the early stages of ovarian cancer. The relapsed form of the disease, however, is resistant to platinum and therefore has a particularly poor prognosis. Additional concerns regarding the use of platinum-based drugs are their toxic side effects and the inability to monitor tumor response to these drugs. The platinum drugs destroy cancer cells by binding to DNA. In this project, we aim to design new rhenium-based drug candidates for the treatment of relapsed platinum-resistant ovarian cancer. Similar to the platinum drugs, these rhenium compounds are designed to bind to DNA. However, we will also leverage the unique properties of rhenium that allow these compounds to be used for imaging tumor response and cancer-cell-specific targeting. The rhenium anticancer drug candidates developed in this project represent significant steps forward in the chemotherapeutic treatment of ovarian cancer, which has not changed significantly during the last 30 years. Critical Problems in Ovarian Cancer Addressed by This Project: This project will address several critical challenges in ovarian cancer treatment and lead to the development of new anticancer agents that, based on the element rhenium, can overcome platinum resistance in relapsed tumors. These compounds will also be designed to selectively target ovarian cancer cells as a strategy to minimize the toxic side effects that usually occur in patients undergoing platinum-based chemotherapy. Furthermore, the rhenium-based drug candidates will have properties suitable for both optical and nuclear imaging. The dual therapeutic-diagnostic nature of these constructs will enable real-time evaluation of in vivo tumor response to the drugs. New Paradigms, Insights, Technologies, and Applications in Ovarian Cancer: A key result of this project will be the development of new ovarian cancer chemotherapeutic agents that are a substantial improvement over the conventional platinum-based drugs. This work will also create a new paradigm for the treatment of ovarian cancer, as it will broadly direct drug discovery efforts to precious metal elements other than platinum. The great therapeutic potential of these elements remains largely untapped, and this project will provide a rationale for understanding these compounds and translating them into clinical treatments. Relevance to the Vision and Mission of the Ovarian Cancer Research Program (OCRP): The project is directly in line with the vision and mission of the OCRP to eliminate ovarian cancer, as it will lead to the development of novel chemotherapeutic agents that will be applied to treating drug-resistant forms of relapsed ovarian cancer. As such, the research in this project will directly help patients, including military personnel and their family members, who have platinum-resistant relapsed ovarian cancer. Because the prognosis for such patients is extremely poor, this project has the potential to save many lives.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710097
Entities
People
- Justin J. Wilson
Organizations
- Cornell University
- United States Army