Group leader, CNRS Research Director (DREx), co-head of the Institute for Clinical Science, Léon Bérard Center, Director of the DEVweCAN LabEx, Director of the Rabelais Institute for Cancer Interdisciplinary Research, deputy Director at the Cancerology Research Center, Lyon, adjunct Professor at the Buck Institute for Age Research, Novato (USA)
Cancerology Research Center, Lyon, France CNRS, France
Left panel: In adults, the dependence relationship between the cell and soluble molecules (called ligands, represented by small red beads) is a way to control cell renewal. These are necessary to the cell’s survival and recognized by proteins at the cell surface, called Dependence Receptors (DR) (light yellow). If the DR is not presented with its ligand, the cell dies (dark red cells).
Right panel: In some cancers, cells escape this control mechanism, either by becoming able to produce the ligand themselves, or by getting rid of the DR. In both cases, they multiply and form tumors.
Modelization of the Dependence Receptor concept
In adults, cell renewal is precisely controlled, notably by a mechanism involving Dependence Receptors in the control of cell death. In certain cancers, cells escape this process, which gives them a supplementary selective advantage to uncontrollably multiply and form tumors. Patrick Mehlen deciphers those mechanisms to offer novel ways to fight cancer.
In adults, cells renewal is precisely controlled. Notably, cells are in dependence relationship with soluble molecules, called ligands: they are necessary for its survival. They are recognized by proteins at the surface of the cell, called Dependence Receptors (DR). If the DR does not “see” its ligand, the cell dies.
In certain cancers, cells are freed of this control mechanism: either by becoming able to produce their ligand themselves or by getting rid of the DR. In both cases, they are not dependent on the ligand anymore to survive and can multiply uncontrollably, producing then tumors.
Understanding those mechanisms is thus crucial to open new and innovative therapeutical avenues by acting on either the ligand or the DR itself to restore its function in cells which lost it.
Deciphering those mechanisms to fight cancer constitutes the core axis of Patrick Mehlen’s research.
Moreover, one of the main objective of Patrick Mehlen and his laboratory is to help the pre-clinical and clinical development of an antibody blocking the RD/ligand interaction. They showed it was important to combine chemotherapeutical or demethylating treatments to potentialise the anti-tumoral effect of the DR/ligand interference.
Today, the selection of the humanised antibody has been achieved and the official pre-clinical program is ongoing. They hope to enter the Phase I clinical trial in 2016.
• 1989-1993 : Undergraduate studies at the Ecole Normale Supérieure (Lyon, France)
• 1995 : Ph. D., University Claude Bernard, Lyon, France, André-Patrick Arrigo's lab
• 1997-1998 : Visiting scientist, Burnham Institute for Clinical Research, La Jolla, USA, Dale Bredesen's Lab
• 1998 : Appointed Group leader at the CGMC, Lyon, France
• Duquesne Price, 2016
• Elected Member of the French Academy of Sciences, 2013
• Advanced Grant from the European Research Council (ERC), 2012
• Fondation Bettencourt Schueller Prize for Life Sciences, 2011
• Laureat of the Pius XI Gold Medal from the Pontifical Academy of Sciences, 2010
• SIlver Medal of the CNRS, 2005
Starting of a clinical trial inspired by Patrick Mehlen’s group results
Jul 2017, Nat Commun.
Sep 2004, Nature