ABSTRACT
The in vivo hollow fibre model was developed by the National Cancer Institute (NCI) in the United States of America (USA) at a time when the number of potential anti-cancer drugs arising from in vitro screening efforts exceeded the available capacity for testing in traditional xenograft models. Updated analysis of the predictive value of the hollow fibre model continues to indicate that the greater the response in the hollow fibre assay, the more likely it is that activity will be seen in subsequent xenograft models. The original 12 cell line hollow fibre panel has been supplemented with histology-specific panels, and we begin here to analyse their utility in predicting activity in subsequent in vivo models. The key goal of using the hollow fibre model as a way to decrease the cost, both financial and in the number of animals used, to evaluate initial evidence of a compound's capacity to act across physiological barriers continues to be reinforced with our enlarging experience.
Subject(s)
Antineoplastic Agents/therapeutic use , Drug Screening Assays, Antitumor/methods , Neoplasms/drug therapy , Animals , Drug Design , Forecasting , Mice , Models, Biological , Neoplasm Transplantation , Predictive Value of Tests , Transplantation, Heterologous , Tumor Cells, CulturedABSTRACT
The introduction of imaging methods suitable for rodents offers opportunities for new anticancer efficacy models. Traditional models do not provide the level of sensitivity afforded by these precise and quantitative techniques. Bioluminescent endpoints, now feasible because of sensitive charge-coupled device cameras, can be non-invasively detected in live animals. Currently, the most common luminescence endpoint is firefly luciferase, which, in the presence of O(2) and ATP, catalyses the cleavage of the substrate luciferin and results in the emission of a photon of light. In vivo implantation of tumour cells transfected with the luciferase gene allows sequential monitoring of tumour growth within the viscera by measuring these photon signals. Furthermore, tumour cell lines containing the luciferase gene transcribed from an inducible promoter offer opportunities to study molecular-target modulation without the need for ex vivo evaluations of serial tumour samples. In conjunction with this, transgenic mice bearing a luciferase reporter mechanism can be used to monitor the tumour microenvironment as well as to signal when transforming events occur. This technology has the potential to reshape the efficacy evaluations and drug-testing algorithms of the future.
