A few new agents emerged from the ASCO 2007 meeting as very real potential players in lung cancer. Probably at the lead of that list, in my opinion, was axitinib (AG-013736, now a Pfizer product). Similar to agents like sunitinib and sorafenib, this is an oral agent that blocks a target called the Platelet-Derived Growth Factor Receptor (PDGFR) and also is a potent, and selective inhibitor of three different receptors in the Vascular Endothelial Growth Factor (VEGF) family: VEGFR-1, VEGFR-2, and VEGFR-3 (scientists are very clever and original with such names, as you can see). As is typical for any complex biological process, there isn’t just one ligand, the protein that fits fits the target, and a single receptor for it, but rather a family of ligands and receptors that act in a coordinated fashion to balance a mechanism like blood vessel and lymphatic channels (the vessels that move lymph, a plasma-based filtering fluid, between lymph nodes). Here’s a basic schema of the VEGF ligands and receptors (VEGFR-2 is the dominant one):
(Click to enlarge)
Axitinib connects to the intracellular, back end portion that has kinase activity, which basically means that it turns on an enzymatic signalling pathway inside the cell with multiple activities, which in this case ultimately promote blood vessel production that can benefit a growing tumor. Like lots of promising drugs, it inhibits cancer cells in test tube and animal models, but more encouragingly, it’s been studied and looks like it has anti-cancer activity human patients with kidney cancers and some other oncology settings. This year, Dr. Joan Schiller, who heads the oncology program at the University of Texas-Southwestern Medical Center and also chairs the ECOG Lung Cancer Committee, presented results of axitinib as a single agent in previously treated patients with advanced NSCLC (abstract here). Read the rest of this entry »
