Extracellular Vesicle MDM2 DNA Cargo: New Methods to Access a Novel Liposarcoma Candidate Biomarker
Abstract
Topic and Military Health Focus Area: This proposal seeks to address the Topic Area of Sarcoma and the Military Health Focus Area of Mission Readiness by addressing a major gap in cancer early detection of recurrence in liposarcoma (LPS). LPS is a devastating cancer that leads to chronic drains on emotional, energetic, and financial resources of military (and civilian) families of LPS patients, thereby negatively impacting on mission readiness of Armed Forces Services LPS patients and members of LPS patient families. Scientific Objectives and Rationale: LPS extrude small particles into the circulation that are known as extracellular vesicles (EV). EVs contain DNA, RNA, and protein cargoes, including a specific DNA (MDM2) that can rise before LPS recurrence is detected by imaging and may therefore serve as a biomarker for recurrence of this most common form of sarcoma. Unfortunately, EV retrieval is a tedious process requiring specialized laboratory approaches. As such, it is not available to use outside of major medical facilities. We have developed a disposable microfluidic chip that efficiently isolates LPS EVs from patient samples to enable EV collection at virtually any medical care facility, including deployment settings or clinics serving civilians. We hope to move this EV isolation device toward clinical translation/utilization by optimizing efficiency and reliability. Accordingly, we propose two inter-related research objectives: (1) further develop this new device for isolating EV and their DNA cargoes, and (2) validate EV MDM2 DNA as a biomarker for early detection of recurrent LPS using this new device. Impact and Applicability of this Research: EVs and their cargoes have received attention because of potential roles as disease biomarkers. If a clinically practical means to isolate EVs could be developed, it would be possible to provide a point-of-care capacity currently lacking in the military arena. Upon isolation, EVs and their cargoes are stable over time and readily transportable to central facilities for rapid EV cargo analysis. The ability to isolate EVs at the point of care would enable more rapid detection of biomarkers even beyond cancers such as LPS, offered here as an initial proof-of-concept to show utility of this novel device. Our long-term goal is to demonstrate the usefulness of this novel device with its point-of-care capacities to benefit military personnel and also civilians. Deployment of this tool, upon optimization, might enable easier detection of EV cargo-based determinants of critical military mission indicators; e.g., exposure to biological or chemical toxins. A patient-related outcome will most likely be achievable within the 4-year funding time of this Congressionally Directed Medical Research Program grant proposal. Within this time frame, we will know if EV MDM2 DNA can function as a biomarker for the early detection of recurrent LPS, and whether or not our new EV isolation device will be ready for evaluation in the field. If these goals can be accomplished, then it may be possible to assess its usefulness to the many other types of cancer patients (both military and civilian) whose tumors also extrude EVs. Impact on FY21 PRCRP Overarching Challenge: The Overarching Challenge that this proposal seeks to address are the critical gaps in LPS early detection and concomitant prompt implementation of potentially curative therapy. This will be accomplished by development of (1) heretofore unavailable novel LPS biomarkers and innovative diagnostic devices that are useful as (2) minimally invasive strategies to (3) detect tumor recurrence at much earlier points in the LPS disease continuum than is currently possible. Relevance of research to active-duty Service Members, Veterans, and other military beneficiaries: There are known risk factors; e.g., Agent Orange, radiation exposure, certain chemicals, and toxins that Service Members may be exposed to occupation
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210531
Entities
People
- Shaurya Prakash
Organizations
- Ohio State University
- United States Army