Focus on relapse

Whether local or distant from the initial site, disease recurrence is primarily associated with treatment resistance.

A better understanding of the mechanisms behind cancer relapse is essential to being able to anticipate relapse, prevent it, detect it as early as possible and treat it effectively. These are essential objectives to improve patient care and definitively eradicate the disease.

To do this, we are developing 3 integrated research programs by addressing the issue of recidivism at 3 levels:

1. Cellular: intrinsic mechanisms of recurrence

coordinated by Céline Vallot and Yves Allory

2. Tissular: extrinsic mechanisms of recurrence

coordinated by Hélène Salmon and Manuel Rodrigues

3. Whole organism: detection and treatment of relapse

coordinated by Elisabetta Marangoni and François-Clément Bidard

Knowing that the genetic aspects of relapse have been the focal point of research in recent years, we wanted to focus our first program on the non-genetic determinants of relapse. To do this, we study the epigenome and the transcriptome, but also transcription by targeting alternative splicing mechanisms and modifications of RNA, translation or cellular metabolism. Program 2 aims to understand the dialogue between the tumor and its microenvironment.

We characterize tumor microenvironments for pathologies that are difficult to treat or hitherto little studied. We study the cellular and molecular dialogue within these niches as well as their dynamics in response to treatment in order to identify new biomarkers and new therapeutic targets. These first two programs are closely linked, due to the interconnection between cancer cells and their microenvironment. They share the same technologies (single or spatial cells) and use common analysis algorithms. The connection with program 3 is mainly based on the development of relevant preclinical models but also on the implementation of biomarkers in tumor samples and the validation of new immunotherapy approaches based on the discovery of specific cancer neo-epitopes.

These 3 programs are supported by a multidisciplinary team of clinicians and researchers. All participate in the care-research continuum so dear to Marie Curie. Their expertise, which extends from the most fundamental aspects (biology but also mathematics, physics, chemistry, etc.) to the most applied (clinical research, quality of life, artificial intelligence, etc.), constitutes the richness of our SIRIC. The involvement of SIRIC patient representatives at the very heart of this team allows us to position ourselves as closely as possible to the needs of patients and their loved ones.

This project is in line with the cancer control strategy carried out by the National Cancer Institute (INCa) for 2021-2030. The expected impacts concern in particular the improvement of relapse prevention, better consideration of tumor prognosis, new therapeutic approaches, a reduction in treatment-related after-effects and progress in terms of quality of life.