Research
Biomarkers for Precision Oncology : A. Thierry

Our team’s objective is to discover predictive and prognostic biomarkers for use in personalized (‘precision’) medicine in oncology. The team’s researchers are currently working on the fundamental and translational projects of clinicians involved in integrative and clinically pertinent research. In this, it benefits from the proximity of the ICM It is also part of the Integrated Cancer Research Site "SIRIC Montpellier Cancer", which combines all of Montpellier’s resources in basic and clinical research in oncology.

We are especially interested in circulating biomarkers. A particular focus is being devoted to the expression of new molecular and genetic markers, notably by the analysis of circulating DNA and RNA Cancerous tumors release DNA (cirDNA) into the bloodstream1; that DNA has been shown to be a biological source for tumor analysis, and as such is a diagnostic tool with significant potential. CirDNA is a breakthrough technology in oncology diagnostics1,2. Not only has its theranostic potential been validated, but it has also shown considerable promise in the longitudinal care of the disease (including the detection of residual disease, the monitoring of treatment efficacy, the demonstration of resistance mechanisms, and the monitoring of disease recurrence, as well as showing possible screening potential) 3.

Our team is amongst those who have contributed the most to demonstrating cirDNA’s potential, by proving the clinical validity and utility of cirDNA analysis for patients with colorectal cancer (CRC). Our  research also works on exploiting cirDNA’s other potentials, including: (i), its use in detecting mutations following targeted therapy4,5,6; (ii), by developing the IntplexTM test (a multi-marker quantitative cirDNA analysis)7; (iii), by proposing the first guidelines for cirDNA pre-analytic8,9; (iv), the impact of epidemiological factors on cirDNA detection10 ; (v), its use in the follow-up of patients with colorectal6, pancreas, breast and bronchial cancers; (vi), its potential prognostic power11; and (vii), its use in a screening tool for a universal cancer test12. In addition to working on the applications of cirDNA as a diagnostic tool in oncology, our team has also long been engaged in basic research programs on cirDNA’s structure, origin and functions13,14, and has demonstrated notably that a large part of cirDNA derives from extracellular neutrophil traps (NETs), either in the presence of infection (such as COVID-19) or of cancer15,16. Recently, our team also discovered the presence in blood of functional circulating mitochondria without cells17.
The team’s program combines basic, technological and translational research. Its current objectives are:

Basic research on:

1. The origins and structures of cirDNA.
2. The implication of NETs in cirDNA release. (E. Pisareva) 
3. The release of cirDNA of mitochondrial origin, and of circulating free mitochondria. (AR Thierry and C. Prevostel)
3. cirDNA kinetics in patient post-surgery.

Technological research on:

1. The standardization of cirDNA analysis.
2. The assessment of mitochondrial gene sequences as biomarkers. 
3. The development of low pass WGS sequencing of cirDNA, from the non-conventionally used single-stranded library.
4. The development of a method of discriminating between cirDNA from cancerous and healthy individuals (Mr. Ychou, A. Adenis).
5. The study and development of circulating mRNA’s as cancer biomarkers (P. Blache)
6. The impact of physical stress on tumor biology (E. Crapez).

Translational research on:

Nine clinical trials are currently underway, following the three trials already completed  (Mr. Ychou, T. Mazard, A. Adenis), which address not only the potentials described above in different types of cancers (colon, rectum, breast, pancreas). One such example is the Panirinox study (T. Mazard), which is the first interventional study in digestive oncology to consider the use of cirDNA analysis for therapeutic decision.   

It should be noted that these studies participated in the research and development of 9 patents, and led to the creation of DiaDx SAS, Montpellier (https://diadx.com/), a start-up offering solutions for the clinical application of liquid biopsy in oncology.