TBR-760, a Dopamine-Somatostatin Compound, Arrests Tumor Growth of Aggressive Non-Functioning Pituitary Adenomas in Mice

TBR-760 (formerly BIM-23A760) is a chimeric dopamine (DA)-somatostatin (SST) compound with potent agonist activity at both DA type 2 (D2R) and SST type 2 (SSTR2) receptors. Non-functioning pituitary adenomas (NFPAs) express both D2R and SSTR2 and, consequently, may respond to TBR-760. We utilized a mouse model with the pro-opiomelanocortin (POMC) gene knocked-out that spontaneously develops aggressive NFPAs. Both genomic microarray and DA and SST receptor mRNA expression analysis indicate that POMC KO mouse tumors and human NFPAs have similar expression profiles, establishing POMC KO mice as a valid model for study of NFPAs. Treatment with TBR-760 for 8 weeks resulted in nearly complete inhibition of established tumor growth, whereas tumors from vehicle-treated mice increased in size by 890 ± 0.7%. These results support the development of TBR-760 as a therapy for patients with NFPA. Transcriptomic analysis was performed on the pituitary tissues from 2 normal mouse, 2 homozygous POMC gene knock-out mouse, 8 heterozygous POMC gene knock-out mouse. The analysis of whole mRNA transcript expression was done by Affymetrix Mouse Genome 430 2.0 Array, a Robust Multichip Analysis was performed on the CEL files, and differential analysis were done with GeneSpring software.