Pancreatic cancer remains one of the most deadly cancers. Very few therapeutics advanced have been achieved in this disease. Over the last few years, several studies have started to elucidate the molecular biology of PDAC including the genomic landscape of the disease, the importance of the stroma and the immunesuppressive environment characteristic of PDAC. One important development in translational research in PDAC is the availability of preclinical models of the disease. This includes genetically engineered mouse models of cancer, patient derived xenografts (aka Avatar models) and organoids. These models are becoming useful for drug screening, biomarker development and personalize medicine. Using Avatar models we identified Nab-paclitaxel as an effective agent in pancreas cancer in contrast to paclitaxel that does not result antitumor effects. We also showed that Nab-paclitaxel disrupts PDAC stroma, an observation, however, has not been confirmed by others. In addition, studies in mouse models revealed the lack of predictability of SPARC expression for clinical outcome. More recently, we have identified demcizumab and palbociclib as potentially effective agents in PDX models as the basis for their clinical development. PDX models have also de potential to be used as a platform for personalizes cancer treatment. In this regard, we are now conducting the AVATAR clinical trial in which patients with advanced cancer are randomized to receive either a conventional treatment or a treatment based on integrating genomic data with AVATAR mouse mode development.
Citation Format: Manuel Hidalgo. Application of PDX models to pancreas cancer research. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA17.