Our team, located in the Cancer Research Center of Toulouse (CRCT), INSERM U1037 (https://www.crct-inserm.fr/en/), is interested in targeted therapies that are used as standard of care for lung cancer harboring oncogenic addictions such as EGFR mutations. Despite the improved clinical outcomes derived from the introduction of EGFR tyrosine kinase inhibitors (EGFR-TKI), the overall prognosis remains unfavorable because of the systematic emergence of resistances. Recent studies have suggested that these resistances may emerge from a small population of drug-tolerant cells that initially resists the treatment by entering a slow cycling state dependent on epigenetic modifications.
Targeting these cells should thus be a new promising approach to hamper the emergence of secondary resistance, however an accurate phenotypic and molecular characterization of this particular state still lack, which is a prerequisite to the development of new therapeutics.
The main objective of the recruited postdoc will be to decipher the mechanisms that lead some lung cancer cells to rapidly adapt and survive to targeted therapies. He/She will develop experimental approaches including cell line set, in vivo models including transgenic mice and Patient-Derived Xenograft (PDX) and will have access to biopsies of patients including solid and liquid biopsies (CTC, Circulating Tumor Cells). In particular he/she will address which signaling pathways and which molecular mechanisms are activated in response to therapy.