Abstract

NCI-Supported Extracellular Vesicle Research: Perspectives and Opportunities

Elisa Woodhouse, Program Director, Division of Cancer Biology, NIH/NCI

Extracellular vesicles (EVs) have emerged in the recent past as important mediators of communication between cells or with the micro- and macro-environments (TME). Nevertheless, NCI portfolio analysis of the past 5 years indicates that while exosome research remains stable it has not expanded in step with its biological significance. Numerous NCI funding mechanisms may be leveraged towards directly or indirectly achieving short- and long-term growth in this research field.  Direct measures include a wide range of training programs or administrative supplement initiatives that can further support current funded EV projects and the next generation of researchers. Furthermore, EV-focused or technology-development NCI funding announcements and ongoing NCI/NIH Programs also provide opportunities for specific aspects of EV research. Indirectly, parallel development and implementation of new NCI initiatives are also being strategized, including a new series of cooperative networks that – broadly speaking – place greater emphasis on the micro-/macro-environments (and numerous TME components such as EVs) as modulators of disease progression. Several programs have been established to comprehensively study and differentiate various stages of disease progression as distinct entities governed by nuanced biological rules and dynamics across the tumor-TME continuum, including the role of the TME as a co-organizer – from early lesions to frank tumors and advanced disease/therapeutic resistance. This recent recalibration in TME emphasis – away from the classical tumor-centric/autonomous dogma will likely further stimulate EV research in different stages of disease progression and as an integral component of tumor-stromal dynamics. Central to this set of objectives are three NCI programs: Translational and Basic Research in Early Lesions (TBEL) focused on risk stratification and understanding the determinants of early lesion evolution; PDAC Stromal Reprogramming Consortium (PSRC) tackling the role of the stroma as a co-organizer of early lesion fate in a disease-specific manner; and Acquired Resistance to Therapy Network (ArtNet) examining the TME response in driving therapy resistance.