Establishment of orthotopic primary cervix cancer xenografts

Abstract

Standard treatment for women who are diagnosed with stage IIB through IVA cervical cancer consists of cisplatin-based chemotherapy and radiation. Current options for patients with recurrent and metastatic disease are limited, and their median overall survival is <12 months. To date, biologic therapy has had little impact on survival, so identification of potential new targets is urgently required to develop novel therapeutic strategies. Developing relevant animal models for human cervix cancer is important to further enhance our understanding of the characteristics of these tumors and for identification and assessment of novel therapies. We have established a panel of orthotopically passaged xenografts (OCICx) by implanting cervix tumor pieces from patient biopsies directly into the cervix of mice. The tumors have been passaged up to five generations, were characterized histologically for tumor and stromal content and, where possible, related to similar measurements in the original patient biopsy. The tumors were found to metastasize to the para-aortic lymphnodes allowing assessment of their metastatic potential. Preliminary studies demonstrate aberrant expression of genes in the Hedgehog (Hh) pathway in the xenografts similar to findings in primary cervix cancers. The OCICx xenografts represent unique models to test strategies for targeting essential pathways in cervix cancer and metastasis.