<p class="MDPI12title"><span lang="EN-US" style="mso-bidi-font-size: 18.0pt;">In vivo and In Vitro Efficacy of Statin Therapy in Combination with Somatostatin Analogues in Advanced Bronchopulmonary Neuroendocrine Tumors
Dyslipidemia may negatively impact progression-free survival in patients with advanced BP-NETs, and atorvastatin therapy could offer some benefit, but further validation is needed.
Where it sits
this study against the rest of the lanreotide corpusSummary and findings
This study evaluated the impact of atorvastatin and lanreotide on progression-free survival (PFS) in patients with advanced bronchopulmonary neuroendocrine tumors (BP-NETs) and assessed the in vitro effects of these treatments. The study found that dyslipidemia was associated with shorter PFS, while atorvastatin therapy showed a positive trend in dyslipidemic patients. The in vitro analysis indicated reduced cell viability and increased apoptosis with combined treatment.
Abstract
<h4>Background: </h4> /Objectives: Metabolic alterations, including dyslipidemia, are increasingly recognized in patients with neuroendocrine tumors and may influence tumor biology and treatment outcomes. However, the clinical relevance of dyslipidemia and the potential impact of lipid-lowering therapies in bronchopulmonary neuroendocrine tumors (BP-NETs) treated with somatostatin analogues (SSAs) remain poorly defined. This study aimed to evaluate the progression-free survival (PFS) in patients with advanced BP-NETs receiving SSAs according to dyslipidemia as well as statin therapy. In addition, an exploratory in vitro analysis was performed to assess the combined biological effect of statins and SSAs. <h4>Methods:</h4> This study investigated the combined effects of atorvastatin and lanreotide therapy both in vitro and in a clinical setting. In NCI-H727 cells, we assessed cell viability, proliferation, apoptosis, DNA damage, and metabolic activity following single and combined treatments. Concurrently, we retrospectively evaluated the impact of dyslipidemia and statin therapy on progression-free survival (PFS) in patients with advanced BP-NETs receiving SSAs. <h4>Results:</h4> Combined treatment resulted in reduced cell viability, proliferation, and ATP production, alongside increased apoptosis and DNA damage, and was associated with impaired cellular energy metabolism compared with lanreotide alone and control conditions. In the clinical analysis, dyslipidemia was associated with shorter progression-free survival (PFS), whereas atorvastatin therapy in dyslipidemic patients showed a positive trend toward improved PFS. <h4>Conclusions:</h4> These findings support the potential relevance of lipid metabolism modulation as an adjunct strategy in advanced BP-NETs, warranting further validation in larger prospective studies and encouraging additional biochemical investigation of the underlying pathways.