Current clinical approaches to treating gliomas and astrocytomas have not significantly improved patient survival, because many brain tumors are refractory to chemotherapy. Previous reports suggest that higher grade human brain tumors have lower adenylyl cyclase activity and/or intracellular cAMP concentrations and that increasing cAMP levels is antiproliferative. Toll et al. investigated the possibility that selective β2-adrenergic receptor (β2-AR) agonists could inhibit growth of gliomas and astrocytomas through elevation of cAMP. In 1321N1 and U118 cell lines, isoproterenol and (R,R′)-fenoterol inhibited cell proliferation, and that effect was blocked by the β2-AR antagonist propranolol. The extent of antiproliferative effect correlated with the level of β2-AR expression and the EC50 for increasing cAMP in these cells. According to information from the Oncomine cancer profiling database, a significant portion of gliomas and astrocytomas express β2-ARs to a greater extent than in normal brain, suggesting that this receptor represents a potential therapeutic target in the treatment of brain tumors. To reduce the cardiovascular risks of β2-AR agonists, the fenoterol analog (R,R′)-ethylfenoterol was suggested as a reasonable lead drug candidate.
See article at J Pharmacol Exp Ther 2011, 336:524–532.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics