Owing to the high genetic heterogeneity of tumors, small number of therapeutic strategies available, and frequent presentation of drug resistance, the prognosis for patients with advanced gastric cancer(AGC) are unsat...Owing to the high genetic heterogeneity of tumors, small number of therapeutic strategies available, and frequent presentation of drug resistance, the prognosis for patients with advanced gastric cancer(AGC) are unsatisfactory. The utility of traditional cancer cell lines in translational research is limited by their poor correspondence to the genomic alterations and expression profiles that occur in actual patient tumors. In the last decade, increasing attention has been given to patient-derived tumor xenografts(PDTXs), which can faithfully recapitulate the histopathology, molecular characteristics, and therapeutic responses of the patient's tumor. However, the widespread development and utilization of PDTXs is restricted by factors such as the timeframe of establishment, lymphoma transformation during passaging, the immunodeficient microenvironment, and pharmacokinetic differences between mice and humans. In this review, we summarize the establishment and characterization of PDTX models for gastric cancer(GC). We then weigh the advantages and limitations of PDTXs when used to evaluate novel compounds, identify effective biomarkers, demonstrate resistance mechanisms, and predict clinical outcomes.展开更多
Patient derived xenograft (PDX) is defined as a growth of patients’ tumor in the xenograft setting. The evolution of cancer model in animal has a century old history. The most single reason that exerted the pressure ...Patient derived xenograft (PDX) is defined as a growth of patients’ tumor in the xenograft setting. The evolution of cancer model in animal has a century old history. The most single reason that exerted the pressure on the traditional animal model of cancer to evolve to PDX is that the traditional models have not delivered as expected and traditional models have not predicted clinical success. In spite of well above 50 drugs developed and approved for oncology over the last several decades, there remains a nirking paucity of clinical success as a reminder that this war on cancer riding on the animal model is far from won. In a backbreaking attempt to analyze the failure, the limitation of the “model” system appeared to be the most rational cause of this shortcoming. It was more of a failure to test a drug rather than a failure to make a drug that stunted our collective growth and success in cancer research. PDX is the product of this age-old failure and its fitness is currently tested in virtually all organ-type solid tumors. This review will present and appraise PDX model in the context of its evolution, its future promise, its limitations and more specifically, the current content of PDX in different solid tumors including breast, lung, colorectal, prostrate, GBM, pancreatic, hepatocellular carcinoma and melanoma.展开更多
文摘Owing to the high genetic heterogeneity of tumors, small number of therapeutic strategies available, and frequent presentation of drug resistance, the prognosis for patients with advanced gastric cancer(AGC) are unsatisfactory. The utility of traditional cancer cell lines in translational research is limited by their poor correspondence to the genomic alterations and expression profiles that occur in actual patient tumors. In the last decade, increasing attention has been given to patient-derived tumor xenografts(PDTXs), which can faithfully recapitulate the histopathology, molecular characteristics, and therapeutic responses of the patient's tumor. However, the widespread development and utilization of PDTXs is restricted by factors such as the timeframe of establishment, lymphoma transformation during passaging, the immunodeficient microenvironment, and pharmacokinetic differences between mice and humans. In this review, we summarize the establishment and characterization of PDTX models for gastric cancer(GC). We then weigh the advantages and limitations of PDTXs when used to evaluate novel compounds, identify effective biomarkers, demonstrate resistance mechanisms, and predict clinical outcomes.
文摘Patient derived xenograft (PDX) is defined as a growth of patients’ tumor in the xenograft setting. The evolution of cancer model in animal has a century old history. The most single reason that exerted the pressure on the traditional animal model of cancer to evolve to PDX is that the traditional models have not delivered as expected and traditional models have not predicted clinical success. In spite of well above 50 drugs developed and approved for oncology over the last several decades, there remains a nirking paucity of clinical success as a reminder that this war on cancer riding on the animal model is far from won. In a backbreaking attempt to analyze the failure, the limitation of the “model” system appeared to be the most rational cause of this shortcoming. It was more of a failure to test a drug rather than a failure to make a drug that stunted our collective growth and success in cancer research. PDX is the product of this age-old failure and its fitness is currently tested in virtually all organ-type solid tumors. This review will present and appraise PDX model in the context of its evolution, its future promise, its limitations and more specifically, the current content of PDX in different solid tumors including breast, lung, colorectal, prostrate, GBM, pancreatic, hepatocellular carcinoma and melanoma.
