Intracellular-signaling tumor-regression modeling of the pro-apoptotic receptor agonists dulanermin and conatumumab.

ABSTRACT: Dulanermin (rhApo2L/TRAIL) and conatumumab bind to transmembrane death receptors and trigger the extrinsic cellular apoptotic pathway through a caspase-signaling cascade resulting in cell death. Tumor size time series data from rodent tumor xenograft (COLO205) studies following administration of either of these two pro-apoptotic receptor agonists (PARAs) were combined to develop a intracellular-signaling tumor-regression model that includes two levels of signaling: upstream signals unique to each compound (representing initiator caspases), and a common downstream apoptosis signal (representing executioner caspases) shared by the two agents. Pharmacokinetic (PK) models for each drug were developed based on plasma concentration data following intravenous and/or intraperitoneal administration

SUBMITTER: Kay BP 

PROVIDER: S-EPMC3487388 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature