Cell population kinetics - experimental methods and their in vivo relevance for human cancer chemotherapy

The value of certain concepts derived from experimental studies of stem cell kinetics are discussed in terms of their clinical relevance. The application of these principles involving treatment for approximately 24 hours on an intermittent basis as soon as bone marrow recovery has occurred, has been shown clinically markedly to increase the safety and selectivity of cancer chemotherapy. Examples are given for treating breast carcinomas, head and neck tumours and bronchogenic carcinomas. In vitro studies with established cell lines have confirmed the observation in tumour-bearing mice that exposure for a 24 hour period results in two types of dose response curves for the stem cell populations, which form the basis for the Kinetic Classification of Antitumour Agents. This simple in vitro system is now being used to classify newer antitumour agents. Attempts to extend these studies to consider stem cells in human tumours are described together with their problems and limitations.