# Harnessing human brain and liver microphysiological systems for testing therapeutics for metastatic melanoma

> **NIH NIH U01** · VANDERBILT UNIVERSITY · 2020 · $1,536,934

## Abstract

Project Summary
The standard for assessing the effectiveness of drugs to treat metastatic melanoma is the patient's response,
but there is a pressing clinical need for a human surrogate model that could support prediction of drug efficacy,
thereby saving the patient from trial and error treatments, and that would ultimately serve as a guide for the
selection of patient-targeted drug therapies. Today, there is significant interest in the use of patient-derived
xenografts (PDXs), in which a patient's tumor is implanted into an immune-deficient mouse, to create in the
mouse a model of the patient's tumor. Unfortunately, this process is slow and expensive and is based upon an
animal microenvironment rather than a human one. Microphysiological systems (MPS), which encompass
organs-on-chips, tissue chips, and engineered organoids, can be constructed using human cells to create an in
vitro microenvironment. The proposed research would build upon a strong collaboration at Vanderbilt
University, the University of Pittsburgh, and the University of Wisconsin to develop powerful MPS to address
the need for models of a patient's response to cancer therapy. This project will study how the tissue
microenvironment affects the growth of metastatic melanoma cells and their response to drugs by using the
Vanderbilt neurovascular unit tissue chip, the Pittsburgh liver-on-chip, and the Wisconsin engineered organoids
for brain and liver, each of which includes multiple cell types. The research will focus on the final stage in the
metastatic cascade – the growth of tumor cells at sites distant from the primary tumor. This growth is governed
by “seed and soil” interaction between the tumor “seed” and the tissue microenvironment “soil.” Instead of
using a mouse as the soil, patients' cancer cells will be planted into the soil provided by brain and liver MPS
constructs derived from human induced pluripotent stem cells. The aims are 1) Implement a common set of
human organ constructs (liver-on-chip, neurovascular unit, and engineered organoid from a single human stem
cell source), 2) Demonstrate successful seeding of these human organ constructs with metastatic cutaneous
melanoma or uveal melanoma cells derived from Vanderbilt and Pittsburgh patients, and 3) Compare the
response to drugs by patients' cancer cells that have been seeded into the organs-on-chips and engineered
organoids with the response to the same drugs by existing PDX lines. This project will provide guidance as to
which in vitro human model might be more predictive of patient outcome when translated to the clinic, based in
part upon the type of tumor, the nature of the patient sample, and the patient genotype. It will also test the
hypothesis that the human MPS devices and models developed at Vanderbilt, Pittsburgh, and Wisconsin will
provide a more realistic, in vitro, three-dimensional human microenvironment to study tumor metastasis than
mouse PDXs. The final phase will be a proof-of-concept demonstrat...

## Key facts

- **NIH application ID:** 9999702
- **Project number:** 5U01TR002383-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** WILLIAM L. MURPHY
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,536,934
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999702

## Citation

> US National Institutes of Health, RePORTER application 9999702, Harnessing human brain and liver microphysiological systems for testing therapeutics for metastatic melanoma (5U01TR002383-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999702. Licensed CC0.

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