New molecular markers of response to medical therapy in acromegaly

The management of pituitary neuroendocrine tumors (PitNETs) is shifting toward a personalized medicine approach, supported by the identification of biomarkers that can guide individualized surgical and medical strategies. In acromegaly, medical therapy with somatostatin receptor ligands (SRLs), dopamine agonists, and GH receptor antagonists represent the cornerstone of treatment in patients with persistent disease after surgery or when surgery cannot be performed. However, therapeutic outcomes are highly variable, reflecting the substantial heterogeneity of somatotropinomas. The classical approach, which considers clinical factors, radiological features, and histological subtypes, continues to play a role but remains insufficient to reliably identify treatment response with high accuracy. New approaches such as those based on functional testing and omics sciences-including genomics, epigenomics, transcriptomics, and proteomics-are showing superiority in identifying determinants of treatment response. Although current evidence is growing, these approaches are still considered in the research field but are slowly being introduced in clinical practice. In this chapter, we review the available molecular and functional markers of response to medical therapy in acromegaly and discuss how to include them in the clinical ground for advancing precision medicine in this disease.