Quantification of the proliferative characteristics of
normal and malignant cells has been of interest to oncologists
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 observation
that significant differences in proliferation characteristics
exist between normal and malignant cells. Initially, cell cycle
analysis was pursued enthusiastically in the hope of generating
information useful for the development of rational
cancer therapy strategies; for example, by allowing identification
of rapidly proliferating tumors against which cell
cycle-specific agents could be used with maximum effectiveness
and by allowing rational scheduling of cell cyclespecific
therapeutic agents to maximize the therapeutic ratio.
Unfortunately, several difficulties have prevented realization
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 anticipated,
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 information
about human malignancies and normal tissues can
be obtained in a timely fashion.