Discovery of Tumor, Treatment Response, and Systems-based EVP Signatures

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Tumor metastasis is a complex, multifactorial process, and identification of the EV determinants of metastatic potential has been made possible by the highly precise and comprehensive EV analytical strategies discussed in related projects ZIA BC 011502, ZIA BC 011942, and ZIA BC 012107. Our studies identifying EV cargo elements that relate to metastatic potential build on and are enabled by the rigorous and comprehensive EV analytical workflows developed in the CCR Translational Nanobiology Section. We are systematically characterizing EV cargo elements across tumor types with varying metastatic potential, using our validated model systems to define mechanisms of pro-metastatic EV production and function. Through collaborations with clinical oncology colleagues at NIH, we are evaluating these discoveries with clinical samples, and correlating EV cargo signatures with treatment responses and disease progression. This integrated approach enables us to identify molecular determinants of metastatic behavior while simultaneously developing clinically applicable monitoring strategies. Moreover, we hypothesize that vascular-, immune-, and stromal-derived EV populations (subsets) that we can identify in liquid biopsies also carry distinct molecular signatures that reflect real-time changes in the tumor microenvironment during treatment. Therefore, we are also using the Section's technological foundation to identify systems-based EV cargo signatures from vascular, immune, and stromal cells that evolve in one way during tumor progression and in another way during treatment responses. By integrating this area of investigation into our clinical and basic laboratory research, we aim to develop more precise methods for monitoring patient responses. By analyzing these dynamic EV signatures, we aim to enable earlier detection of treatment resistance and identification of adaptive therapeutic strategies.