The human tumour xenograft--a valid model in experimental chemotherapy?

Abstract

The chemotherapeutic response of a series of patients with bronchial carcinoma has been compared with the response of their xenografts established in immune-suppressed mice. The in situ endpoint of growth delay in subcutaneous tumours was the main parameter used to assess xenograft response, but clonogenic cell survival studies were also performed to assess the extent of cell kill associated with in vivo responses. Histology, chromosome analysis and demonstration of ectopic hormone production indicated that the xenografts retained human morphology and functional behaviour. Clinical response was assessed by serial measurement of metastases. The chemotherapeutic validity of xenografts is supported by this study in which 21 separate responses in 16 patients and their respective xenografts were similar. Metastases regressed completely in 5 out of 7 patients with oat cell carcinoma. Xenografts derived from these were also highly responsive to similar chemotherapy. In contrast, minimal responses were observed in xenografts established from two chemoresistant patients. One large cell anaplastic, 3 squamous and 4 adenocarcinomas were universally chemoresistant in patients and their xenografts. It is concluded that the bronchial carcinoma xenografts broadly retained human morphology and functional behaviour, and reproduced the pattern of chemotherapeutic response of their source tumours. The present work suggests that the incorporation of human tumour xenografts into drug development programmes is justified, although their usefulness in a predictive capacity to select appropriate chemotherapy for individual patients remains limited.