Mutational signatures in PDXs for improved understanding of drug response and companion biomarkers identification

Genomic DNA editing is a continuous process that occurs during the entire cell life span. The type and frequency of these modifications can be related to the physiological or pathological activity of intrinsic mechanisms such as DNA surveillance and repair or to extrinsic events that may induce an alteration of DNA sequence by exposure to agents that directly or indirectly induce accumulations of DNA alterations. In the past few years, large-scale analyses have revealed mutational signatures across human cancer types. These signatures can be used as markers of defective internal processes, such as DNA repair deficiency, or external exposures, such as carcinogens, like tobacco, or genotoxic therapies such as radiation and chemotherapy.

Our TumorGraft platform, a collection of 1500 patient-derived xenografts generated from more than 50 different types of cancer, is one of the most comprehensive preclinical oncology platforms worldwide and aims to recapitulate the variety of the patient population and tumor biology complexity. This platform is currently used to evaluate the efficacy of new drugs, and all our models are very well characterized at the molecular level, including whole transcriptome, proteomics and phospho-proteomics, quantification, and genomic variation calls.