Cell kinetics and the management of malignant disease

Cell kinetics technology and its application to study human malignant disease is reviewed. The use of radiolabelled DNA precursors has generated evidence that tumors do not necessarily proliferate faster than their normal tissue counterparts. The pulse tritiated thymidine labelling index has largely been accepted as a crude measure of overall proliferative activity, and conflicting data have emerged with regard to its prognostic significance for response of leukemias and solid tumors to chemotherapy. Cytokinetic strategies of recruitment and synchronization have lacked appropriate documentation and have not been demonstrated to yield superior clinical results. Introduction of DNA flow cytometry has significantly enlarged our understanding of tumor cell kinetics and facilitated data collection on clinical material. While serial measurements of cellular DNA content are ideally suited to analyze the effects of antitumor compounds on cell cycle distribution, they do not provide cytodynamic information on cell cycle phase transit times. Furthermore, the implications of even reversible cell cycle blocks for cell viability are not readily apparent. Recent cytochemical developments may permit the distinction between cycling and non-cycling cells as well as characterization of tumor vs. normal cells through the use of concurrent analysis of DNA and RNA or protein content. In order to test the biological importance of tumour cell kinetics for the treatment of human neoplasma, a complete cytokinetic description of tumour and normal cell kinetics should be attempted using DNA flow cytometry as backbone to be supplemented by measurements of growth fraction and cytodynamic parameters. This information should be related to histopathology, stage and site of disease and to prognosis along with already appreciated clinical or laboratory variables of prognostic importance. Thus the feasibility of cell kinetics strategies such as recruitment, synchronization and normal tissue protection should be tested and clinical advantage over conventional combination chemotherapy demonstrated.