Team LEHMANN-CHE

Pathophysiology of Breast Cancers

This axis aims to decipher the molecular and transcriptional mechanisms by which NFAT (Nuclear Factor of Activated T cells) factors control the invasive, migratory, and metastatic plasticity of tumor cells. Drawing on models of aggressive cancers, notably triple-negative breast cancer and pancreatic cancer, we analyze how NFAT activity is modulated by the cellular context and the tumor microenvironment to drive pro- or anti-metastatic programs.

The goal is to identify the gene networks, microRNAs, and epigenetic regulators under the control of NFAT factors, and to understand how their deregulation promotes tumor dissemination, colonization of distant organs, and treatment resistance. This axis integrates cell biology approaches, transcriptomics, and in vivo models in order to link fundamental mechanisms to tumor phenotypes.

Ultimately, this work aims to reveal novel biological vulnerabilities and to identify innovative therapeutic targets capable of selectively inhibiting the NFAT-dependent programs involved in the metastatic progression of aggressive cancers.

This axis explores the role of extracellular vesicles (EVs) as natural vectors of intercellular communication and as innovative therapeutic platforms for the development of RNA therapies. We study how certain EVs carry antitumor signals capable of modulating the invasive, proliferative, and metastatic behavior of cancer cells, and how these properties can be exploited for therapeutic purposes.

The axis builds on the development of RNA therapy strategies, including microRNAs, siRNAs, or mRNAs, with a particular focus on combinatorial approaches aimed at simultaneously targeting multiple key oncogenic pathways. This strategy rests on the hypothesis that coordinated action on molecular networks is necessary to achieve robust and durable biological effects in aggressive cancers.

We develop and evaluate EV engineering methods, as well as alternative delivery systems, in order to optimize the loading, stability, and functional efficacy of therapeutic RNAs in vitro and in vivo. This axis aims to position EVs as next-generation vectors for personalized RNA therapies, capable of curbing tumor progression and metastatic dissemination in clinical settings that still lack effective treatments.