Liver Radiotheranostics Group

Projects

Utilizing Light-Activatable Nano-Particles to Enhance the Efficacy of Y-90 Microspheres in Liver Cancer

Goal

This project aims to harness the high energy and bright Cerenkov radiation emission from yttrium-90 (Y-90) microspheres to stimulate light-activatable nano-particles to enhance the efficacy of Y-90 radioembolization. This previously untapped physical source of tumoricidal activity can introduce photodynamic therapy (PDT) to previously optically impenetrable liver tumors, enhancing efficacy in high-risk patients.

Understanding the Biological Underpinnings of Response or Resistance to Y-90 Radioembolization

Goal

While tumor transcriptomic signatures, cell differentiation, and liver disease etiology likely inform HCC outcomes, their relationship to Y-90 radioembolization treatment is unknown. We seek to delineate dose response curves to Y-90 microspheres in a wide range of human HCC cell lines and tumoroids spanning the diverse genetic and transcriptomic landscape of HCC. These results will inform potential biomarkers of response or resistance to Y-90 radioembolization.

Developing Patient-Derived HCC Tumoroids to Enhance the Relevance and Translatability of Preclinical HCC Investigation

Goal

There is currently a dearth of biologically relevant HCC animal models that are amenable to transarterial administration of Y-90 microspheres. In addition, the vast majority of immortalized human HCC cell lines are derived from tumors developed in a background of viral liver disease, which doesn’t reflect the burgeoning increase in HCC from nonalcoholic fatty liver disease (NAFLD) in the West. This underscores the need for patient-derived models to ensure bench-to-bedside relevance of preclinical investigations. Tumoroids, which faithfully replicate the original tumor histological architecture, heterogeneity, biomarker, and genetic signatures, can be generated from patient tumor tissues obtained by image guided needle biopsies. In close partnership and collaboration with investigators in the Digestive Diseases Research Cores Center (DDRCC) at WUSTL, we have begun efforts to establish lines of HCC tumoroids suitable for preclinical investigations from our patient population.

Our People

The lab, led by interventional radiologist Christopher Malone, MD, is an interdisciplinary team merging clinical and basic science fields to optimize outcomes and enhance our understanding of patient response to image guided therapies for liver cancer.

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