Speeding towards individualized treatment for pancreatic cancer by taking an alternative road22/03/2018
From bench to the bedside: Inserm U1068 Research lab22/03/2018
As mentioned above, a major obstacle for efficient treatment of PDAC is its molecular heterogeneity reflected by the variable clinical evolution. The starting point of this project was precisely the heterogeneity observed in the clinical outcome of PDAC patients, the variable survival time after diagnosis and a strong difference in the sensibility of tumors to treatments. We hypothesized that “deep and systematic” studies by using “Omics” approaches should allow us to i/ classify tumors; ii/ identify the most effective and specific targets for each patient, and iii/ to identify clinically useful biomarkers. This project will be able to explore many promising approaches focused on comparing by “Omics” approaches of a cohort of PDTX (Patient-Derived Tumor Xenograft). The extensive multiOmic profiling revealed two subtypes with distinct clinical outcomes. These subtypes uncovered specific alterations in DNA methylation and transcription as well as in signaling pathways involved in tumor-stromal cross-talk. The analysis of these pathways indicates therapeutic opportunities for targeting both compartments and their interactions. In particular, we demonstrate that inhibiting NPC1L1 with Ezetimibe, a clinically available drug, might be an efficient approach for treating a subgroup of PDAC. Said in other words, this type of “without a priori” approach is the only strategy that may identify clinically relevant markers, if they exist.