Lung cancer is the major cause of cancer-related death in France and worldwide. In the past few years, patients with specific genetic alterations such as mutations in the EGFR gene (about 15% of lung adenocarcinomas, 45% in non-smokers), have benefited from treatments called targeted therapies such as Erlotinib, Gefitinib or more recently Osimertinib, which show excellent response rates in most of these patients. However, almost all of them will be confronted with resistance mechanisms that will rapidly limit the clinical benefit initially obtained. The origin of this resistance is still largely unknown. Recent studies have shown that a small proportion of tumor cells have the ability to adapt to treatment by entering a state of pseudo-dormancy, allowing them to tolerate the presence of the drug the time necessary to develop these resistance mechanisms. Targeting these cells could therefore be a promising new therapeutic approach to slow down or even prevent the emergence of resistances, but this cellular state remains poorly characterized, making the development of new treatments impossible.
Our team has recently identified a mechanism used by lung tumor cells to allow them to survive anti-EGFR targeted therapies. Our goal is now to better understand the behavior of these cells in response to treatment in order to identify their weaknesses and to find a treatment able to eradicate these dormant cells which are most likely at the origin of the relapse in patients.
The LUNG-RESIST project is coordinated by Prof. Julien MAZIERES and Dr. Olivier CALVAYRAC. It has received support of €100,000 from the Toulouse Cancer Health Foundation.