A MULTIPARAMETER APPROACH TO CELL CYCLE ANALYSIS AS A STANDARD TOOL IN ONCOLOGY DRUG DISCOVERY - Flow Cytometry in Drug Discovery and Development - page 95

A MULTIPARAMETER APPROACH
TO CELL CYCLE ANALYSIS AS
A STANDARD TOOL IN ONCOLOGY
DRUG DISCOVERY

C ARMEN R AVENTOS -S UAREZ AND B YRON H. L ONG

5.1 INTRODUCTION

In the early part of the twentieth century, the drug discovery process focused first on
animals to prove a pharmacological effect. However, focus shifted to cells as cell
culture became more practical, expedient, and cost-effective and as animal welfare
concerns increased [1]. A more recent shift to molecular targets occurred for almost
the same reasons, but mainly for cost and high throughput [2]. Another factor
impacting this shift was the rapid discovery of new physiological functions afforded
by advances in molecular biology. These advances gave the opportunity to screen
compounds directly against designated target molecules in a high-throughput mode
and as single molecules tested across parallel assays [3]. Cellular and animal models
have since then evolved into parallel development as the new animal testing models
moved into xenografts and genetically engineered cancer models [4].
Because of these advances, it is almost forgotten that biological macromolecules
can have affinities for any small molecule. The role of specific affinities and the
possibility of unexpected cross-reactivity for any biological macromolecule require
broader focus, especially at the cellular level. In most cases, cross-affinities will be so
small that they can afford to be ignored. However, when a compound with a strong
affinity for a specific therapeutic target also has an unexpected affinity for another