Primary human non-small cell lung and pancreatic tumorgraft models--utility and applications in drug discovery and tumor biology

Abstract

The number of therapeutic options for lung and pancreatic cancer is increasing because of the identification of new druggable molecular targets and development of new drug combinations. Reproducible, biologically relevant in vivo pre-clinical models are critical for this effort. The generation of patient-derived tumor xenografts has proven useful for integrating drug screening with biomarker discovery, discovering fundamental information in tumor biology, prioritizing drugs for clinical investigation, and personalizing treatments for these tumors. The protocol described in this unit details how to establish a direct in vivo subcutaneous primary tumorgraft and maintenance passages. The predictive value of a tumorgraft platform to guide personalized medicine is illustrated with the case of a patient with refractory advanced non-small cell lung cancer (NSCLC). The outcome of a patient for whom their own pancreatic tumorgraft revealed a remarkable sensitivity to mitomycin C based on a PALB2 mutation is also detailed.