Future treatment strategies of aggressive pituitary tumors

Abstract

While surgery remains the first-line treatment of most aggressive pituitary adenomas, medical therapy is important as second-line or adjunctive therapy in a large proportion of patients. Dopamine agonists (DAs) are the best treatment for prolactinomas, but when DAs are not tolerated, new somatostatin receptor subtype 5 (SSTR(5)) inhibitors may offer an alternative in the future. Unfortunately, these are unlikely to be effective in DA-resistant prolactinomas. In acromegaly, the existing somatostatin analogs, octreotide and lanreotide, will remain the medical treatment of choice for the foreseeable future. There is an urgent need for medical therapies in Cushing's disease, and the SSTR(5) analogs could offer an effective treatment in a proportion of patients within the next few years. Finally, the medical management options for non-functioning pituitary adenomas are also very limited, and a new chimeric agent with activity towards dopamine receptors, SSTR(5) and SSTR(2) may help reduce adenoma recurrence in the future.

Fig. 1

Effect of SSTR₅-specific analog on prolactin secretion from DA-susceptible and DA-resistant human prolactinomas. From Jaquet et al. [1]

Fig. 2

Pro-apoptotic effects of different somatostatin analogs in human somatotroph tumors. From Ferrante et al. [7]

Fig. 3

[³H]-thymidine uptake inhibition from cell culture of 38 non-functioning pituitary adenomas by cabergoline, octreotide and dopastatin. From Florio et al. [20]