SAT-067 Evaluating Drug-Induced Effects on Cell Viability in Acromegaly Using a Patient-Derived 3D Culture Model

Abstract Disclosure: Y. Tsujimoto: None. A. Ishida: None. H. Shichi: None. N. Yamamoto: None. Y. Motomura: None. Y. Oi-Yo: None. Y. Sasaki: None. M. Suzuki: None. S. Urai: None. H. Bando: None. M. Yamamoto: None. M. Takahashi: None. G. Iguchi: None. N. Inoshita: None. S. Yamada: None. W. Ogawa: None. H. Fukuoka: None. Background: Several predictive markers for drug selection in acromegaly (Acro) are known, most based on hormonal suppression effects. Acro is characterized by excessive growth hormone secretion and clinical tumor effects due to the high prevalence of macroadenomas, making it essential to predict drug responsiveness for tumor shrinkage. In oncology, patient-derived 3D tumor culture systems have proven to be reliable tools for evaluating drug responses, bridging the gap between in vitro experiments and clinical studies. This study aimed to develop a similar model for Acro to assess drug responsiveness and evaluate its potential for predicting treatment outcomes. Methods: Tumor specimens from 27 Acro patients (median age: 46 [range: 36-56] years; female/male ratio: 13/14) were collected postoperatively and processed into 3D cell culture, as previously described (Tsujimoto Y, et al. J Endocr Soc. 2021; bvab055.). The culture cells were treated with therapeutic agents—octreotide (Oct) 10 nM, cabergoline (Cab) 10 nM, pasireotide (Pas) 10 nM, or vehicle—under standardized conditions. The drug response was defined as a statistically significant reduction in cell viability compared to vehicle-treated controls, as measured by the RealTime-Glo™ MT Cell Viability Assay, which provided real-time feedback on the drugs' cytotoxic effects. Fisher's exact tests and Mann-Whitney U test evaluated associations between responsiveness and clinical or histological factors. Results: Among the 27 cases, 9 (33%) responded to Oct, with an association observed in tumors with T2WI hypointensity on MRI (p = 0.04). The responsiveness to Cab was observed in 9 cases (33%), with an association in patients who responded to the bromocriptine test (p = 0.04). Pas exhibited the highest response rate (11 cases, 40%), which was associated with sparsely granulated tumors (p = 0.04).Discussion:The use of a 3D tumor culture system derived from Acro patients provided insights into drug-specific responsiveness, aligning with previously identified predictive factors for Oct, Cab, and Pas. However, it is important to note that most previously reported predictive factors focus primarily on biochemical remission. The assay's ability to measure real-time cell viability represents a significant advancement in evaluating treatment efficacy, particularly for tumor shrinkage, which has historically been challenging to predict. Integrating this approach into clinical practice, particularly for postoperative residual cases, could enable personalized medicine by refining drug selection based on tumor characteristics. Further validation in larger cohorts and prospective clinical trials is warranted to establish its broader applicability and cost-effectiveness. Presentation: Saturday, July 12, 2025