Inhibition of DDX3 Activates a Type I Interferon Response in Osteosarcoma

Authors: Jecenya TapiaCabrera, Dylan Gafarian

SUNY Campus: Farmingdale State College

Presentation Type: Poster

Location: Old Union Hall

Presentation #: 46

Timeslot: Session C 1:45-2:45 PM

Abstract: Osteosarcoma (OS) is a highly aggressive malignant bone tumor that primarily affects adolescents and young adults, with approximately 1,000 cases reported annually. Despite advancements in chemotherapy, survival rates for OS patients remain poor, highlighting the urgent need for novel targeted therapies. OS lacks a clear driver mutation, making tumor-specific treatments challenging. However, recent studies have identified DDX3, an RNA helicase involved in RNA metabolism, as a promising biomarker in OS. DDX3 has been implicated in the regulation of the Type I Interferon (IFN) response, a critical component of the innate immune system. Our research explores whether targeting DDX3 can induce a Type I IFN response as a potential therapeutic strategy for OS. We investigate the effects of RK-33, a small-molecule inhibitor that binds specifically to DDX3, sequestering it in the cytoplasm. By disrupting DDX3 function, we hypothesize that RK-33 can trigger an antiviral-like immune response, leading to tumor suppression. This study aims to determine whether modulating DDX3 activity can activate the Type I IFN pathway, ultimately enhancing anti-tumor immunity in OS. Understanding the interplay between DDX3 inhibition and immune activation may provide new insights into OS pathogenesis and therapeutic intervention. Given the current lack of targeted treatments for OS, our research presents a novel approach that could contribute to the development of effective immunotherapeutic strategies for this aggressive malignancy.