Patient-derived tumor xenografts as models for personalized medicine

Cancer is the most common cause of death in the world. Most patients can be resistant to chemotherapy,so, developing of new therapeutic strategies seems essential.Interestingly, in spite of enormous failure rate and lethal side effects, chemotherapy still finds the widest application in terms of treatment amongst all established therapies.Any particular therapy can prove to be effective in some patients but ineffective in others with some experiencing adverse drug reactions resulting in patient morbidity and mortality, while some remain unaffected. Reasons include intrinsic or acquired multi-drug resistance, DNA poly-morphisms and most importantly the presence of inter-tumor heterogenic sub-populations, responding to radio-, chemo-,and- targeted therapies differently amongst different individuals within the same cancer type.This inter-individual difference in response to drug treatment thus strongly commends a paradigm shift from “One Drug Fits All” strategy towards “Personalized Medicine”. Today, the traditional standard approach“one-dose-fits-all” to drug development and clinical therapy has been ineffective, as it incurs all risks of subsequent drug toxicities and treatment failures. The studies have shown that the average response rate of an anti-cancer drug is the lowest at 25%, suggesting that 75% of patients with cancer are over-dosed and will potentially suffer from an adverse drug reaction. The ultimate goal of personalized medicine is to furnish the proper treatment to the right person at the right time. On the other hand, with the ability to forecast disease risk or presence before clinical symptoms appear, personalized medicine offers the opportunity to act on the disease through early intervention.

Our research team, by producing PDX (patient-derived xenograft) models, enables our colleague physicians to apply the animals such as mice as a model for human cancer research. The potential applications of PDX are vast and include the identification of new treatment targets and optimal treatment schedules, the analysis of tumor response, the pre-clinical evaluation of drug combinations and the identification of bio-markers and mechanisms of drug resistance. Our PDX models, produced by engrafting the human tumor sections into immune-suppressed mice, are valuable tools for testing new anticancer agents and new drug combinations. Before initiation of chemotherapy, our colleague physicians by analyzing the xenograft model results will be able to select the appropriate therapeutic options for the specific treatment of cancer.