Corticorelin acetate, a synthetic corticotropin-releasing factor with preclinical antitumor activity, alone and with bevacizumab, against human brain tumor models.
BACKGROUND: Corticorelin acetate (CrA) is a synthetic form of corticotropin-releasing factor that is currently undergoing clinical trials in the treatment of peritumoral brain edema (PBE). This study preclinically investigated its potential as an antitumor agent against human brain tumor xenografts. MATERIALS AND METHODS: The in vivo efficacy of CrA as a single agent and in combination with the antiangiogenic agent, bevacizumab, was examined in three different patient-derived human brain tumor xenografts implanted orthotopically (intracranially) or subcutaneously in athymic mice. RESULTS: CrA significantly increased the lifespan of mice implanted orthotopically with two different pediatric brain tumor xenograft models. In one of these tumor models, the combination of CrA with bevacizumab produced a therapeutic outcome superior to that found using either of the two agents alone. CONCLUSION: The application of CrA for the treatment of PBE likely involves its activity as an anti-angiogenic agent, which may be one possible mechanism to explain its observed preclinical antitumor activity against orthotopic human brain tumor models. Additional studies to investigate other possible mechanisms of action are underway.
Gamez, I; Ryan, RP; Keir, ST
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