Gaps and paths forward in cancer pharmacology and translational research.

As drug development costs continue to rise, there is a need to reframe how drug efficacy is evaluated in preclinical models to reduce the rate of false positives. The "valley of death" refers to the gap between bench research and clinical translation. In particular, oncology chemotherapies have the highest rate of drug failure compared to other drug classes. While there has been progress in overall cancer survival, some cancers and patient populations still have a poor prognosis. To bridge the gaps of drug failure and aid underserved patient populations, drug translation cannot be viewed as a purely linear process, but one in which continual refinement is used to create more efficacious drug candidates. Additionally, pharmacokinetic-pharmacodynamic modeling could prove instrumental in better understanding drug efficacy in cellular models and in evaluating clinical translation potential with greater accuracy. The path forward in clinical pharmacology is to view drug development and efficacy as a dynamic process rather than a purely linear fashion. This review discusses traditional pharmacodynamic and pharmacokinetic evaluation methods, as well as pharmacokinetic-pharmacodynamic models of tumor growth inhibition.