Tumor Effect‐Site Pharmacokinetics: Mechanisms and Impact on Efficacy

Abstract

Biologics, particularly monoclonal antibodies, form a rapidly growing field of cancer therapeutics. These molecules have exquisite specificity for their targets, thereby reducing off‐target effects. However, there are inherent challenges in managing the pharmacokinetics of biologics. In this chapter, focus on how mechanisms of distribution and efficacy play out at the site of action for cancer biologics: the tumor. The chapter first describes the distribution of antibodies and other macromolecules in tumors comprising the effects of tissue physiology, drug properties, and their interaction. A brief review of fluid transport in healthy and tumor tissues is followed by mechanisms that determine antibody distribution. The chapter details how this distribution ultimately impacts efficacy. It overviews cell‐killing mechanisms leading into a discussion on how particular delivery issues impact each of these strategies.