Multimodal Treatment Consisting of Ferroptotic Agent and Chimeric TRAIL as a Second-Line Therapy for Ovarian Peritoneal Carcinomatosis
Abstract
Ovarian cancer is the most common cause of death among all gynecological neoplasms. Ovarian peritoneal carcinomatosis (OPC) is a frequent terminal evolution of ovarian cancer and is regarded as a lethal condition. In the past, OPC was considered a terminal disease stage, but over the past two decades, the therapeutic techniques of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) have been developed. However, although CRS treated with HIPEC has been associated with an increased response rate, complete responses have been rare and recurrences are common. In this grant application, we are developing a multimodal treatment consisting of the FDA-approved ferroptotic agent artesunate and TRAIL as a second-line therapy. Currently, we are establishing tumoroids of OPC and investigate the mechanism of the synergistic induction of apoptosis caused by the integration of signal transduction pathways in organoids of OPC. Although ferroptosis is considered a distinctive form of cell death compared to other types of death such as apoptosis and it is known to result from iron-dependent accumulation of lipid peroxides rather than caspase activation, our studies have shown that ferroptosis interplays with apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2021
- Accession Number
- AD1146190
Entities
People
- Yong J Lee
Organizations
- University of Pittsburgh