USEOFFLOWCYTOMETRYTOSTUDY DRUG TARGET INHIBITION IN LABORATORY ANIMALS AND IN EARLY-PHASE CLINICAL TRIALS - Flow Cytometry in Drug Discovery and Development - page 147

USEOF FLOWCYTOMETRYTOSTUDY
DRUG TARGET INHIBITION IN
LABORATORY ANIMALS AND IN
EARLY-PHASE CLINICAL TRIALS

D AVID W. H EDLEY

7.1 OVERVIEW

This chapter reviews the use of flow cytometry to study pharmacodynamics at the
single-cell level during the transition from preclinical to early-phase testing of novel
agents, including the potential for individual patient dose optimization based on
pharmacodynamic monitoring. Although the emphasis is on cancer, particularly
hematological malignancies where flowcytometry is uniquely suited, consideration is
given to underlying principles that are applicable to inflammatory and autoimmune
disorders and to solid tumors. Particular emphasis is placed on the use of panels of
phosphospecific antibodies to monitor agents that act to inhibit signal transduction
pathways, because of the importance of these agents and the unique capability of flow
cytometry to monitor signaling networks at the single-cell level. However, this
chapter touches on a broad range of applications to illustrate a field that is rich, and
only partially explored.