The Role of Receptor-Ligand Interaction in Somatostatin Signaling Pathways: Implications for Neuroendocrine Tumors

Simple Summary The tissue expression of somatostatin receptor (SSTR) subtypes in neuroendocrine tumors (NETs) holds paramount significance with far-reaching diagnostic and therapeutic implications. SSTRs contribute significantly to localizing NETs, aiding in advanced imaging techniques such as somatostatin receptor scintigraphy and PET scans. Elevated SSTR expression often aligns with less aggressive tumors, impacting tumor grading and influencing treatment decisions. Therapeutically, SSTRs serve as pivotal targets for treatments like targeted radiotherapy and synthetic somatostatin analogs (e.g., octreotide), commonly employed to inhibit hormone secretion and suppress tumor growth. Tailoring treatment strategies based on SSTR subtype expression enhances therapeutic efficacy. SSTR expression serves as a valuable prognostic indicator, predicting treatment response. While challenges like tumor heterogeneity persist, ongoing research explores promising avenues, including combination therapies. In conclusion, a nuanced understanding of SSTR expression in NETs is indispensable for precise diagnosis and the development of tailored therapeutic interventions, offering the potential for improved patient outcomes.Abstract Neuroendocrine tumors (NETs) arise from neuroendocrine cells and manifest in diverse organs. Key players in their regulation are somatostatin and its receptors (SSTR1-SSTR5). Understanding receptor-ligand interactions and signaling pathways is vital for elucidating their role in tumor development and therapeutic potential. This review highlights SSTR characteristics, localization, and expression in tissues, impacting physiological functions. Mechanisms of somatostatin and synthetic analogue binding to SSTRs, their selectivity, and their affinity were analyzed. Upon activation, somatostatin initiates intricate intracellular signaling, involving cAMP, PLC, and MAP kinases and influencing growth, differentiation, survival, and hormone secretion in NETs. This review explores SSTR expression in different tumor types, examining receptor activation effects on cancer cells. SSTRs' significance as therapeutic targets is discussed. Additionally, somatostatin and analogues' role in hormone secretion regulation, tumor growth, and survival is emphasized, presenting relevant therapeutic examples. In conclusion, this review advances the knowledge of receptor-ligand interactions and signaling pathways in somatostatin receptors, with potential for improved neuroendocrine tumor treatments.