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.
Patient-Derived Tumor Xenograft (PDX) models for cancer research have come into focus lately due to their predictivity for clinical outcome and utility in biomarker development. As super immunodeficient strains such as the CIEA NOG mouse® became available, PDX of hematological malignancies could be established to a similar extent as their solid tumor counterparts. Within the last 2 years, Oncotest has developed 48 acute leukemia PDX models and started to develop a similar panel for different Non-Hodgkin Lymphomas.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