CCR 20th Anniversary Commentary: Determining a Pharmacokinetic/Pharmacodynamic Relationship for Sunitinib—A Look Back

Abstract

The article by Mendel and colleagues, published in the January 1, 2003, issue of Clinical Cancer Research, described their novel preclinical approach to developing a thorough understanding of the exposure–activity relationship for sunitinib, a multitargeted receptor tyrosine kinase inhibitor being developed for oncology therapy. This work successfully set exposure guidelines to identify a biologically active dose in early clinical trials. Clin Cancer Res; 21(11); 2415–7. ©2015 AACR. See related article by Mendel et al., Clin Cancer Res 2003;9(1) January 2003;327–37

Efficacy and safety of sunitinib in Japanese patients with progressive, advanced/metastatic, well-differentiated, unresectable pancreatic neuroendocrine tumors: final analyses from a Phase II study

“…3). The C trough values of total drug (which is the summation of sunitinib and its active metabolite) observed at Cycle 1–4 in most patients were above 50 ng/ml, which is the estimated minimum concentration to achieve target inhibition based on the preclinical data (19); the steady-state C trough values of total drug after Cycle 5 were not monitored.…”

Anti‐angiogenic activity of thienopyridine derivative LCB03‐0110 by targeting VEGFR‐2 and JAK/STAT3 Signalling

“…Several VEGFR‐2 inhibitors, such as sunitinib, are currently being used in the clinic. However, sunitinib also inhibits platelet‐derived growth factor receptor (PDGFR), c‐Kit and Flt‐3 . To develop small‐molecule anti‐angiogenic agents, we screened our in‐house compound libraries and identified thienopyridine derivative LCB03‐0110 as a potent inhibitor of angiogenesis.…”

Advances in identification and validation of protein targets of natural products without chemical modification

“…99,101 MALDI-MSI was used for in vivo validation of the interaction between a compound and target protein using sunitinib, a receptor tyrosine kinase inhibitor (RTKI), using known target receptor tyrosine kinases (RTKs). [102][103][104] This study provided direct evidence that MALDI-MSI could be a powerful means for validating interactions between a compound and its target protein in vivo. Furthermore, this could be a promising method for providing information on label-free compounds with regard to absorption, distribution, metabolism, and excretion (ADME), and on metabolites and target proteins aer in vivo administration to patients.…”