# New tools for understanding metastasis through tissue resident cells: enabling an Extensive Medicine strategy for metastatic disease

> **NIH NIH DP2** · RESEARCH INST OF FOX CHASE CAN CTR · 2020 · $2,805,000

## Abstract

Project Summary
Cancer remains a menace because of our inability to tackle metastatic disease. Metastasis is the culmination of
a long history of interactions between cancer cells and the microenvironments of invaded tissues, resulting in a
disease that is highly heterogeneous intra- and interpatient. For this reason, the currently available treatments
for metastatic disease show limited efficacy since a large fraction of tumors develop escape strategies.
Therefore, targeting a new type of cancer commonality could lead to new treatments for a significant portion of
metastatic patients. It has been recognized for more than a century that the invaded tissue (“soil”) plays a role
in metastasis as important as that of the metastatic cells (“seed”). However, technical limitations have kept most
research focused on the primary disease or intrinsic properties of the “seed”. Yet colonized organs are not
passive; they contain complex sets of cell types which must interact with invading cells to allow invasion and
expansion. I propose a new conceptual framework in which molecular changes arising in metastasis-interacting
resident cells (MiRCs) are a general feature of metastasis and could serve as new therapeutic targets. As such
alterations may be common across cancer types and patients, targeting them could lead to Extensive Medicine
approaches to complement Precision Medicine. To fulfill this vision, a new in vivo strategy to label and track
interactions between metastatic cells and MiRCs is required. We have developed such a system, based on
synthetic Notch (SynNotch) receptors. We have used this new SynNotch MiRC Labeling System, and our
expertise in liver biology (the liver is the most common site of metastasis across cancer types), to label and
isolate metastasis-interacting hepatocytes (MiHs). By using this approach, our first goal is to identify the
molecular alterations in MiHs across multiple murine and human liver metastatic models; candidate genes will
be tested for ability to reduce metastasis. In addition, to realize the full potential of this novel conceptual
framework, we will generate a genetic toolbox to allow the analysis of any MiRC in any metastatic model. Finally,
we will invert the SynNotch System to track metastatic cells which have interacted with a tissue resident cell of
choice; this will help address questions such as whether metastatic progression occurs sequentially or by
developing from the primary tumor, and whether invasion of lymph nodes is a prerequisite for metastasis. This
proposal aims to provide the conceptual and experimental foundation for a new approach to tackle metastatic
disease based on the molecular characterization of MiRCs using our new SynNotch in vivo System. Tools and
techniques established here can also be applied in metastatic cells to aid in resolving fundamental questions
about the metastatic process. Finally, these same tools and techniques can be used in other diseases or
biological processes invol...

## Key facts

- **NIH application ID:** 10002762
- **Project number:** 1DP2CA258224-01
- **Recipient organization:** RESEARCH INST OF FOX CHASE CAN CTR
- **Principal Investigator:** Joan Font-Burgada
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,805,000
- **Award type:** 1
- **Project period:** 2020-09-08 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10002762

## Citation

> US National Institutes of Health, RePORTER application 10002762, New tools for understanding metastasis through tissue resident cells: enabling an Extensive Medicine strategy for metastatic disease (1DP2CA258224-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10002762. Licensed CC0.

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