Abstract A028: Precise monitoring of osteosarcoma patients by noninvasive assessment of matrix metalloproteinases activities in plasma extracellular vesicles

Abstract Osteosarcoma (OS) is the most prevalent bone cancer in children, characterized by aggressive primary tumors and high metastatic potential. Current treatment protocols involve a combination of neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy, tailored based on histological grade and metastatic risk. Identifying metastatic lesions through routine imaging significantly impacts treatment outcomes, highlighting the need for innovative diagnostic tools for timely monitoring. Noninvasive in vitro diagnostics, analyzing circulating tumor components like tumor-derived extracellular vesicles (EVs), would offer promise for monitoring treatment responses in pediatric sarcomas. Matrix metalloproteinases (MMPs) play a crucial role in tumor progression by degradation of the extracellular matrix; thus, recent research has focused on understanding their functional roles by profiling their proteolytic activities. Tumor EVs are crucial in transporting MMPs to facilitate invasion and metastasis, making them suitable surrogate for noninvasive profiling of MMP activities. Herein, we introduce an innovative OS EV MMP Activity Assay to assess MMP activities in OS patients noninvasively. This assay evaluates six different combinations of surface markers on OS EVs and OS-associated MMPs, generating a unique profile for each patient. Using a logistic regression model, an OS EV MMP Activity Score is generated from the most effective combinations. This Score has shown excellent performance in distinguishing between metastatic and localized OS. In a longitudinal study of six OS patients undergoing treatment, the Score strongly correlated with treatment response as measured by routine imaging. The assay represents a significant advancement in harnessing tumor EVs for diagnostics, providing a noninvasive, quantitative, and reliable approach to assess MMP activities in solid tumors. Citation Format: Junseok Lee, You-Ren Ji, Hyoyong Kim, Zhao Chen, Ryan Zhang, Diego Banuet, Yusef Mathkour, Kenny Vo, Steven Jonas, Yazhen Zhu, Hsian-Rong Tseng. Precise monitoring of osteosarcoma patients by noninvasive assessment of matrix metalloproteinases activities in plasma extracellular vesicles [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A028.