The Oxford English Dictionary defines language as “The method of human communication, either spoken or written, consisting of the use of words in a structured and conventional way.” This section of CCR FOCUS describes various ways in which anticancer agent pharmacodynamics is being studied, with the goal of clinical translation. Pharmacodynamics is the study of drug action—and all the factors that modify that. Given a new agent in development, the clinical oncologist wants to know the response rate and toxicity, the translational oncologist wants to know whether the drug engaged its target and for how long, and the pharmacologist wants to generate a complex model describing the interrelationship of various factors to treatment effect or toxicity. The authors in this CCR FOCUS section address various aspects of these equations. With William Douglas Figg and David R. Newell as Guest Editors, the papers show us the complex network that underlies the action of every drug and offer hope that we can eventually understand the factors that influence drug action well enough to use them in the clinical setting to improve cancer treatment. We learn in this CCR FOCUS that modern methodologies are available to explore and possibly understand why some patients have side effects when others do not—the kind of science that could lead to further drug discovery. We learn new strategies for determining whether a drug distributes to the tumor tissue (imaging) and whether we can demonstrate a molecular effect in a circulating tumor cell (allowing repeated study and avoiding biopsy). And, we learn that once we know a drug can affect a target, we still are far from having reliable, validated, and widely useable pharmacodynamic assays to prove it. Oncologists and pharmacologists will have to work together, speaking a common language, to make continued progress. We see this section in CCR FOCUS as a step in that direction. As always, we hope that this section will inform those who are interested but not expert, and challenge and encourage those who are expert in the field.
Figure 1.
Pharmacodynamics can be defined as “what the drug does to the body” which includes activity and toxicity, and underlying mechanisms and molecular determinants. The drug effect on both normal cancer cells may be on-target (T) or off (Off-T). Genetic variation (PG) affects both pharmacokinetics (PK) and pharmacodynamics (PD). In contrast, PK is “what the body does to drug”: absorption, distribution, metabolism and excretion (ADME) and underlying mechanisms and determinants.