Bypassing the Resistance Mechanisms of the Tumor Ecosystem by Targeting the Endoplasmic Reticulum Stress Pathway Using Ruthenium- and Osmium-Based Organometallic Compounds: An Exciting Long-Term Collaboration with Dr. Michel Pfeffer.

Fiche publication


Date publication

septembre 2021

Journal

Molecules (Basel, Switzerland)

Auteurs

Membres identifiés du Cancéropôle Est :
Dr GAIDDON Christian, Dr GROSS Isabelle, Dr JUNG Alain, Dr ROMAIN Benoit, Dr MELLITZER Georg, Dr VENKATASAMY Aina, Dr DELHORME Jean-Baptiste


Tous les auteurs :
Gaiddon C, Gross I, Meng X, Sidhoum M, Mellitzer G, Romain B, Delhorme JB, Venkatasamy A, Jung AC, Pfeffer M

Résumé

Metal complexes have been used to treat cancer since the discovery of cisplatin and its interaction with DNA in the 1960's. Facing the resistance mechanisms against platinum salts and their side effects, safer therapeutic approaches have been sought through other metals, including ruthenium. In the early 2000s, Michel Pfeffer and his collaborators started to investigate the biological activity of organo-ruthenium/osmium complexes, demonstrating their ability to interfere with the activity of purified redox enzymes. Then, they discovered that these organo-ruthenium/osmium complexes could act independently of DNA damage and bypass the requirement for the tumor suppressor gene to induce the endoplasmic reticulum (ER) stress pathway, which is an original cell death pathway. They showed that other types of ruthenium complexes-as well complexes with other metals (osmium, iron, platinum)-can induce this pathway as well. They also demonstrated that ruthenium complexes accumulate in the ER after entering the cell using passive and active mechanisms. These particular physico-chemical properties of the organometallic complexes designed by Dr. Pfeffer contribute to their ability to reduce tumor growth and angiogenesis. Taken together, the pioneering work of Dr. Michel Pfeffer over his career provides us with a legacy that we have yet to fully embrace.

Mots clés

ER stress pathway, TP53, cancer, cell death, chemotherapy, cisplatin, immunotherapy, osmium, photodynamic therapy, resistance, ruthenium

Référence

Molecules. 2021 Sep 4;26(17):