Quantification of the proliferative characteristics of normal and
malignant cells has been of interest to oncolo- gists and cancer
biologists for almost three decades. This interest stems from (a) the
fact that cancer is a disease of uncontrolled proliferation, (b) the
finding that many of the commonly used anticancer agents are
preferentially toxic to cells that are actively proliferating, and (c)
the observa- tion that significant differences in proliferation
characteristics exist between normal and malignant cells. Initially,
cell cycle analysis was pursued enthusiastically in the hope of gener-
ating information useful for the development of rational cancer therapy
strategies; for example, by allowing identi- fication of rapidly
proliferating tumors against which cell cycle-specific agents could be
used with maximum effec- tiveness and by allowing rational scheduling of
cell cyc- specific therapeutic agents to maximize the therapeutic ratio.
Unfortunately, several difficulties have prevented realiza- tion of the
early promise of cell cycle analysis: Proliferative patterns of the
normal and malignant tissues have been found to be substantially more
complex than originally an- ticipated, and synchronization of human
tumors has proved remarkably difficult. Human tumors of the same type
have proved highly variable, and the cytokinetic tools available for
cell cycle analysis have been labor intensive, as well as somewhat
subjective and in many cases inapplicable to humans. However, the
potential for substantially improved cancer therapy remains if more
accurate cytokinetic infor- mation about human malignancies and normal
tissues can be obtained in a timely fashion.
