# Decellularized Extracellular Matrix Scaffolds to Engineer the Dormant Landscape of Microscopic Colorectal Cancer Liver Metastasis

## TL;DR

This paper introduces a new model using liver scaffolds to study dormant colorectal cancer metastases, which could help improve cancer treatments.

## Contribution

A novel in vitro model using decellularized liver extracellular matrix to induce and study dormancy in colorectal cancer liver metastases.

## Key findings

- Decellularized liver extracellular matrix scaffolds induce dormancy in colorectal cancer cells.
- Dormant cells show slowed proliferation and chemotherapy resistance.
- The model mimics dormancy and recurrence, offering insights for therapeutic development.

## Abstract

Recurrent liver‐metastatic colorectal cancer contributes to high mortality. Recurrence occurs when dormant, microscopic residual disease survives initial treatment to escape dormancy. In their dormant, microscopic state within the liver, these metastatic lesions are undetectable by clinical diagnostic imaging until they form overt, chemoresistant metastases. Therefore, understanding the molecular mechanisms underlying dormancy in colorectal cancer liver metastases is a significant knowledge gap, motivating the engineering of nuanced in vitro models of disease. The current work presents an engineered model of liver‐metastatic colorectal cancer dormancy. Decellularized extracellular matrix (dECM) scaffolds are used to provide microscopic colorectal cancer cell clusters with a biomimetic, 3D liver‐specific architecture to colonize. Combined with nutrient deprivation and low dose chemotherapy, liver dECM significantly promotes dormancy, which manifests as slowed proliferation, nutrient/chemo‐dependent G1/S and ECM‐driven G2/M cell cycle arrest, diminished tumorigenicity, and robust chemotherapy resistance. The engineered dormancy signature is reversible, mimicking dormancy escape. The dECM‐based model of engineered dormant colorectal cancer liver metastasis is crucial for advancing knowledge of dormancy induction and reversal, to improve therapeutics and patient survival.

Decellularized liver extracellular matrix scaffolds provide a platform to study dormant liver‐metastatic colorectal cancer. They induce reversible dormancy, in combination with nutrient depletion and low dose chemotherapy, through cell cycle arrest and chemotherapy resistance. Mimicking dormancy and recurrence, this model can be used for mechanistic and therapeutic discovery with the goal of improving patient response and survival.