Human tumour xenografts in radiotherapeutic research

Abstract

The radiation response of human tumour xenografts has been shown to vary considerably among tumours of different histological types, tumours of the same histological type and cell subpopulations of single tumours. There is encouraging evidence that the radiation response correlates with clinical responsiveness when xenografts are exposed to single radiation doses and single cell survival in vitro or growth delay in vivo is used as endpoint. If subsequent research supports this conclusion, human tumour xenografts may be useful in studies aimed at (a) elucidating the underlying mechanisms for intertumour differences in radiation response and (b) developing short-term in vitro assays for clinical radiosensitivity testing. However, there are at least three main disadvantages with xenografts as models for human cancer. Firstly, the volume-doubling time is usually shorter than for tumours in man. Secondly, the vascular system and the supporting stromal elements originate from the host. Thirdly, host defence mechanisms may be active against xenografts. The radiation response of xenografts may be influenced by these three aspects and hence fail to reflect clinical responsiveness, especially when exposed to fractionated irradiation or when local tumour control is used as endpoint.