A pioneering scientific program to better understand the epigenetic biology of tumors and find new treatments.
Project leader: Sophie Postel-Vinay
Epigenetics is a new advance in the fight against cancer. It is a promising field that focuses on changes in gene activity. Epigenetics allows the cell to adapt to stimuli and the external environment without changing its genetic code or introducing mutations, allowing it to evolve and adapt. Gustave Roussy's emerging epigenetics program is led by Dr. Sophie Postel-Vinay, a research physician in the Department of Therapeutic Innovation and Early Trials (DITEP) and the Inserm unit "Molecular Predictors and New Targets in Oncology" and is destined to become a future Medical-Scientific Program (MSP) of the Institute.
"DNA, the genetic code that programs the cell, is similar to the letters in the words of a book. For a story to be understandable, the words must be spelled correctly and spaced, and the text must have proper punctuation and chapters. This layout, with indications of which chapters to read and which not to read, corresponds to epigenetics. In the cancer cell, the DNA accumulates spelling mistakes, the punctuation is altered, and the cell does not always read the right sentences or chapters," explains Dr. Sophie Postel-Vinay, leader of the emerging epigenetics program at Gustave Roussy. Thus, epigenetics allows the caterpillar to transform itself into a butterfly, by changing the chapter reading, it allows the tumor cell to transform itself to become resistant to treatments, or to be invisible to the immune system for example. Thus, epigenetics influences all characteristics of cancer and plays a key role in tumor initiation, progression and treatment resistance.
Characterizing tumors from an epigenetic perspective
Epigenetics has recently been recognized as a major feature of cancer. Reprogramming the epigenetic landscape is a promising field, especially in difficult-to-treat cancers, but also to overcome resistance or prevent relapse.
However, the understanding of epigenetics in solid tumors is still in its infancy. As clinical successes remain rare, there is an urgent need to translate the fundamental knowledge of this rapidly evolving field into concrete clinical applications, such as new molecular diagnostics and targeted therapies for the benefit of patients. The understanding of epigenomic alterations combined with genomic characteristics, cell microenvironment and its reprogramming, integrated with individual clinical data, is one of the most promising therapeutic strategies for cancer treatment in the era of personalized medicine and precision immuno-oncology.
After being studied in preclinical and cellular models, the development of new technologies and single cell analysis now allows for a better characterization of epigenetics in tumor samples.
The emerging epigenetics program has two main objectives:
- To understand how epigenetic alterations can be targeted by targeted therapies by focusing initially on diseases where they are present in all cells and at the origin of the disease: sarcoma induced by the transcription factor EWS-WT1 and histone H3K27M mutant gliomas.
- To explore how epigenetic deregulation contributes to tumor evolution, in terms of heterogeneity, plasticity, adaptability and resistance to therapy.
Designing new therapeutic options and epigenetic drugs
Epigenetics are considered the next wave of therapeutics in oncology. Drugs that target epigenetic processes have been around for more than 20 years and have demonstrated efficacy in hematological diseases. But they have failed to demonstrate similar results in solid tumors, requiring better treatments, development methods and/or a better understanding of tumor epigenetics.
The final goal of the emerging epigenetics program is to deploy/develop early clinical trials. It also aims to implement molecular profiling techniques focused on the epigenetic landscape of tumors, in particular to optimize epigenetic drug development and identify biomarkers of sensitivity or resistance.
In particular, the emerging program aims to identify at least one therapy targeting SWI/SNF defects and implemented in a clinical trial, as well as a therapy targeting the EWS-WT1 transcription factor.
To launch this promising program, Sophie Postel-Vinay's research team has received a starting package of €250,000 from the generosity of Gustave Roussy donors.