Introduction

There has been a longstanding belief that measurements of cell proliferation should be useful in the management of cancer patients. Many cytotoxic drugs are more active against proliferating cells than nonproliferative ones and in the early 1970s Skipper and others suggested that response to chemotherapy of experimental tumours was related to their proliferative activity (Skipper, 1971). Further, clinical observations suggested that rapidly proliferating types of tumour (e.g. germ cell tumours and high-grade non-Hodgkin's lymphoma) are generally more responsive to chemotherapy and radiotherapy. These observations led to a plethora of studies investigating the relationship between cell kinetic parameters and response of tumours to chemotherapy and to schemes to try and take advantage of cell kinetics in the design of treatment schedules (Price et al., 1975). However, as early as 1977, Steel wrote ‘although many clinical oncologists claim that their thinking has been influenced by research on tumour growth kinetics, it is hard to point to clear advances attributed to anything more than inspired clinical experimentation’ (Steel, 1977). The lack of impact of cell kinetics on tumour treatment during this period was due to a variety of factors, including technical limitations in measuring cell proliferation in individual clinical tumours and to a failure to appreciate the degree of heterogeneity present in such tumours. Even up to the present day, it is difficult to point to real advances in patient management based on a knowledge of cell-proliferation-related parameters. This failure is still partly due to technical limitations in measuring cell proliferation in individual tumours and also to the failure to standardize the methods that are available.