Detecting epigenetic biomarkers in the blood for non-invasive precision oncology

Introduction

The detection of circulating tumor DNA allows for non-invasively retrieving tumor molecular profiles and following disease evolution. These approaches promise optimal and individualized management of patients with cancer. However, despite remarkable progress, several technological obstacles still limit liquid biopsy's widespread application.

Challenges in Detection

Detecting small fractions of tumor DNA released when the tumor burden is reduced remains a challenge. Samples collected at early stages or during treatment may contain less than one mutant copy per milliliter of plasma, which is below the detection limit of current technologies.

Moreover, detectable recurrent mutations do not cover all patients. It is therefore necessary to develop new, more sensitive, but also more informative tools.

Project Goals

My goal is to develop new methods for detecting epigenetic markers from peripheral blood to establish more efficient non-invasive diagnostic tests and disease monitoring. Targeting the cancer epigenome, which contains a myriad of somatic alterations that do not modify the DNA sequence and cover cases without detectable mutations, will achieve increased sensitivity.

These markers could become decisive in detecting residual disease and early stages of multiple forms of cancer.

Proposed Approaches

I will develop approaches to:

1. Analyze circulating DNA methylation profiles at unique and repeated sequences.
2. Identify circulating DNA cells of origin using nucleosome footprint.
3. Analyze transcripts associated with circulating extracellular vesicles.

Ultimately, a single test integrating DNA methylation profiles, fragmentation patterns, and EV-associated transcripts from the same plasma sample will be developed.

Implications

This project has both fundamental and biomedical implications: it will generate in-depth knowledge of the biology of circulating non-genetic tumor biomarkers and lead to the development of more efficient non-invasive diagnostic tests adapted to all types of cancers, based on the universality of these factors.