Development and validation of in vitro methods for assaying cancer stem cell responses to therapeutic challenge

Cancer remains a serious life-threatening problem and the therapies currently available are not always able to prevent its recurrence or spread. Recent work suggests that only a small fraction of the total cancer cells, the cancer stem cells, is responsible for the growth of cancers. We will develop assays that effectively monitor the actions of drugs on cancer stem cells whilst avoiding involvement of animals.

The concept of cancer stem cells (CSCs) has recently been the focus of much experimental investigation and several reports now indicate that selective survival of CSCs may be responsible for tumour recurrence after therapy. A prevailing current view is that valid information concerning CSCs can be obtained only by work with fresh tumour cells transplanted to murine hosts. With the increasing need to assay existing and new therapeutic agents for actions on CSCs, a large increase in animal use is expected unless suitable surrogate in vitro assays can be developed. We present evidence that stem cell patterns similar to those present in human tumours in situ are generally retained in malignant cell lines. In order to reduce or eliminate the use of animals in stem cell studies, we propose to investigate a wider range of cell lines, for use together with analytical techniques developed in pilot work, to develop, validate and scale up in vitro assays of CSC responses to therapeutic challenge.