3D spheroids derived from single cells for discovering stochastic patterns behind metastasis

Introduction

Metastasis remains accountable for 9 out of 10 fatalities within cancer disease. However, the mechanisms governing the onset of metastasis are far from being fully understood. Notably, metastases are predominantly clonal and arise from a single cell.

Project Overview

3DSecret will investigate metastasis from a radically new perspective, with the overarching goal of unravelling stochastic patterns at the single-cell level with predictive and prognostic capacity.

Importance of the Study

Critically, defining the hallmarks of metastasis from holistic studies of single circulating tumour cells (CTCs) will dissect tumour heterogeneity. This has the power to revolutionise cancer treatment and diagnosis. This will pave the way for game-changing discoveries in what is one of the holy grails of modern clinical science.

Methodology

To achieve our goal, 3DSecret will use a set of key enabling technologies including:

1. Microfluidics
2. Nanosensors
3. Genomics
4. Artificial Intelligence (AI)

Microfluidics will drive the isolation of single CTCs from whole blood samples of 60+ metastatic breast cancer patients. These will be grown on-chip to form 3D spheroids, thus allowing comprehensive genomic and transcriptomic studies of single-cell origin while bypassing the errors typically introduced by single-cell genome amplification.

Data Integration

The genomic and transcriptomic data will be combined with:

• Clinical information
• Single-cell growth profiles
• Dynamic metabolomic analyses obtained by the use of nanosensors and SERS

This integration aims to develop a multimodal AI analytical tool capable of identifying unknown patterns driving metastasis.

Risk and Potential Impact

The bold assumption that there could be stochastic patterns driving metastasis, cancer evolution, and malignancy makes the approach of 3DSecret exceptionally high-risk, high-gain. We are confident that such a breakthrough would lead to a major paradigm shift with significant implications in biology, physics, disruptive technologies such as AI, and critically, in the medical arena and patient care.