Establishment of murine basal cell carcinoma allografts – a potential model for preclinical drug testing and for molecular analysis

Dysregulated hedgehog (HH) signaling has been found in numerous cancers, suggesting that therapeutic targeting of this pathway may be useful versus a wide range of cancers. Basal cell carcinoma (BCC) is an excellent model system for studying the influence of the HH pathway on carcinogenesis because aberrant activation of HH signaling is crucial not only for the development of but also the maintenance of BCC. Genetically engineered BCC mouse models provide one important tool for the study of the biology of human BCCs and for evaluating therapeutic interventions, as these mice produce multiple genetically defined tumors within a relatively short period of time. However, these models remain expensive and cumbersome to use for large-scale preclinical drug testing. Here we report a method for growing allografts from murine BCC tumors in NOD/SCID mice. These allografts develop faster and reproduce the histology, immunophenotypes, and response to at least one anti-BCC drug of the parental autochthonous tumors from which they arise. Therefore, the allograft model provides a practical model for (i) studying BCC carcinogenesis and (ii) initial preclinical screening for anti-HH pathway and other anti-BCC drugs.