Theory and practice of clinical pharmacodynamics in oncology drug development

Semin Oncol. 2016 Aug;43(4):427-35. doi: 10.1053/j.seminoncol.2016.07.001. Epub 2016 Jul 26.

Abstract

The clinical development of molecularly targeted cancer therapies is enhanced by proof of mechanism of action as well as proof of concept, which relate molecular pharmacodynamics to efficacy via changes in cancer cell biology and physiology resulting from drug action on its intended target. Here, we present an introduction to the field of clinical pharmacodynamics, its medical and laboratory aspects, and its practical incorporation into clinical trials. We also describe key success factors that are useful for judging the quality of clinical pharmacodynamic studies, including biopsy quality and suitability, specimen handling, assay fitness-for-purpose, and reagent quality control. This introduction provides not only context for the following articles in this issue, but also an appreciation of the role of well-conducted clinical pharmacodynamic studies in oncology drug development.

Keywords: Assay fitness-for-purpose; Biopsy sample quality; Biopsy surrogate tissues; Reagent quality control.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents / pharmacokinetics*
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / metabolism
  • Biopsy
  • Chemistry Techniques, Analytical / methods*
  • Drug Design
  • Drug Discovery
  • Humans
  • Imatinib Mesylate / pharmacology
  • Molecular Targeted Therapy / methods
  • Neoplasms / drug therapy
  • Reproducibility of Results
  • Specimen Handling / methods*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Imatinib Mesylate