Personalized primary tumor xenograft model established for the pre-clinical trial to guide postoperative chemotherapy

Abstract

Despite of the fact that a large amount of therapeutic agents have been developed for cancer treatment, we are still sometimes in a dilemma of choosing a most effective regimen for individual. With the reference of several recent researches, positive clinical correlations have been identified with primary tumor xenografts models, but limitations in existed models reveals a need for improvement. Over the past decade, conceptual progress has been made that tumors had increasingly been recognized as organs in which ostensibly normal cells as well as cancer cells participate actively in tumorigenesis by creating the “tumor microenvironment”. Herein, we propose a hypothesis based on this novel conception that if transplanted as an organ, tumor implantation in nude mice would conserve most approximated biological traits with improved success rate, which make personalized tumor xenograft model practical for pre-clinical trials as substitutes for each patient. In our pilot study, intact tumor bloc was applied in implantation to evaluate this notion. As a result, 107 xenografts from all 20 patients of gastric cancer were transplanted successfully. Pathological comparison confirmed that no differences between xenografts and primary tumors while the therapeutic response to two chemotherapeutic agents, docetaxel and pemetrexed, exhibited differently. In conclusion, applying personalized primary tumor xenograft model derived from freshly excised tumor in pre-clinic trails would potentially lead to a more effective customized chemotherapy.