Patient-derived Xenografts of Hematological Malignancies: Model Systems for Drug Development and Tumor Biology Research

MessageThis Webinar is over
Date Apr 14, 2016
Time 11 am EDT
Cost Free
Online
In recent years, there have been multiple efforts in the establishment and characterization of large collections of Patient-Derived Tumor Xenograft (PDX) models for cancer research. Although this model system was developed already in the late 1980´s, it has come into focus lately due to its predictivity for clinical outcome and utility in biomarker development. PDX models mainly retain the histological and genetic characteristics of the donor tumor and remain stable across passages. They preserve cell-autonomous heterogeneity thereby representing very well the molecular landscape of the corresponding disease. Since triple immune deficient mouse strains like NOD/Shi-scid/IL-2Rγ null (NOG) mice were made available to the scientific community; PDX of hematological malignancies could be established to a similar extend as their solid counterparts. Despite the incontrovertible advantages of PDX as preclinical models in drug development, pharma research faces a high failure rate combined with rising research and development costs of new drugs particularly in early clinical development. In view of success rates below 5% for innovative cancer drugs, improvements in model development are urgently needed.
Within the last 2 years Oncotest and Taconic have partnered to develop 48 acute leukemia PDX models and started to develop a similar panel for different Non-Hodgkin Lymphomas. The comparison with cell line-derived in vivo models reveals significant advantages of the PDX approach as the latter represents the molecular diversity more in detail, mimics the clinical signs of hematological malignancies more realistic and most importantly mirrors sensitivity towards standard of care in a direct comparison with the donor patient´s clinical outcome. The group strongly believes that the hematological PDX platform is a robust and predictive tool to address translational challenges in oncology research.
Key learning points:
  • How hematological patient-derived xenograft (PDX) models are established
  • How more super immune deficient mouse models have advanced development of hematological PDX models
  • Why hematological PDX models are more translational than cell line-derived models
  • How hematological PDX models can be employed in drug discovery and development

 


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