Tumour response to chemotherapy in animals that have been treated with the same drugs prior to tumour implantation: A model for studying host effects on apparent drug resistance

Abstract

Summary The outcome of cancer chemotherapy is determined by an interplay of multiple factors between the host, the tumour, and the drugs administered. Most studies have emphasised the development or selection of drug resistant tumour cells. However, repeated drug treatment of the host may lead to changes (e.g. in pharmacokinetics, host defences, etc.) which can influence the subsequent response of the tumour. In this study, we present a model to investigate the role of the host in the development of drug resistance. A drug is administered repeatedly to animals prior to tumour implantation, and tumour response is then evaluated following treatment with the same drug in pretreated and control animals.To illustrate the method, cyclophosphamide was administered weekly for 4 weeks to C3H mice before implantation of the KHT tumour. Tumour growth delay was then compared after one further treatment of cyclophosphamide in this group of animals to that in control mice which had not received the cyclophosphamide pretreatment. Our results indicate that cyclophosphamide produces only a small effect on the host in this system, but the model is a potentially useful one to investigate the contribution of the host in the acquisition of drug resistance.

A Possible Correlation Between Growth-Factor Sensitivity and Response to Mitoxantrone Treatment in a Murine Myeloid Leukaemia (SA7HD) Cell Line

“…Repeated treatment in vivo mimics the clinical situation better and may be more suitable for investigating drug-resistance mechanisms. It has been stated that since clinical drug resistance often follows repeated treatment, the use of animals that have been pretreated with the same drug prior to tumour implantation may be a good model for studying host effects on apparent drug resistance (7).…”