T Renno’s team / I Coste’s Group

The search for targeted therapies is of strategic importance in the fight against cancer. The MAP kinase pathway is frequently over-activated in cancer. We have identified a new class of molecules, including the tool molecule EI-52, that inhibit the interaction of the ERK MAPK with its partners, independently of its kinase function, and which induce apoptosis in cancer cells in vitro, ex vivo, and in vivo. Moreover, cancer cells killed by EI-52 produce factors that leverage an anti-tumoral immune response.

We are currently studying the nature of the perturbations induced by EI-52 in ERK’s protein complexes, as well as their biological concequences in terms of apoptosis and immunogenicity in vitro and in vivo. Since there exists a variability in the sensitivity of cancer cell lines and human tumors to EI-52, we will search for molecular determinants of cancer cell response to ERK interaction inhibitors in fresh human cancer tissue.

Overall, this work should reinforce our understanding of the mechanisms underlying the activity of agents that target the protein complexes associated to ERK, which represent a novel approach in cancer.