Abstract B032: Expanding the geographic reach of functional precision oncology through prediction of therapy response with patient-derived tumoroids
Authors: Luciana Harumi Osaki, Tiago Goss dos Santos, Stefano P. Clerici, Celso A. Mello, Tiago Felismino, Gabriel O. Santos, Rodrigo G. Taboada, Virgilio S. Silva, Samuel Aguiar, Felipe Jose Coimbra, Adriane G. Pelosof, Angelo B Brito, Rubens Chojniack, Paula N.V.P. Barbosa, Denisse Esther Mallaupoma-Camarena, Adrhyann J.S. Portilho, Queila C. Dias, Isadora Rattes, Patricia Gama, Rachel S.P. Riechelmann, Vilma R. Martins
Journal: Cancer Research (2025)

Abstract Effective treatment for advanced and metastatic tumors remains a major clinical challenge. Chemotherapy has an objective response rate of 40%, and reliable predictive biomarkers to guide treatment are lacking. Global implementation of Functional Precision Oncology (FPO) offers a promising, personalized approach to predicting tumor response, with potential to improve patient outcomes, optimize resource use, and promote equity across diverse geographic regions. This study aims to establish and validate a functional testing platform using gastrointestinal (GI) patient-derived tumoroids (PDTs) to predict tumor vulnerabilities to standard-of-care (SOC) therapies. In January 2023, the Brazilian National Ethics Committee approved the present prospective, observational clinical study. Biopsies were collected from metastatic lesions of patients with colorectal, pancreatic, and gastric adenocarcinomas, neuroendocrine pancreatic tumors (PNETs), and advanced gastric adenocarcinomas. Isolated cells were embedded in basement extracellular matrix and cultured in media tailored to each tumor type. The PDTs were exposed to SOC drugs, and cell viability was assessed. Drug sensitivity was evaluated by comparing the growth rate (GR) of each PDT to the median GR of PDTs from the same tumor type. PDTs with GR values above the third quartile were classified as resistant, while those b.elow were considered sensitive. Patient tumor responses to SOC therapies were evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST), with outcomes categorized as partial response (PR), stable disease (SD) or progressive disease (PD). Current success rates are 67% (8/12) for colorectal, 69% (11/16) for gastric, and 85% (6/7) for pancreatic adenocarcinomas. PNETs remain challenging, with 26% (4/15) of cultures showing temporary growth and 13% (2/15) establishing permanent cultures. Immunohistochemistry and immunofluorescence confirmed that PDTs retained similar morphology and marker expression as their matched tumors. Fourteen colorectal, fourteen gastric, six pancreatic adenocarcinomas, and two PNETs were treated with SOC drugs. Treatment responses were highly reproducible across biological replicates (Spearman correlation 0.87 to 0.95, p &amp;lt; 10^-6) and demonstrated heterogeneity between PDTs. Treatment response predictions (resistant or sensitive) for six PDTs from adenocarcinomas (three colorectal, one pancreatic, one gastric) and one PNET were correlated with patient clinical outcomes (PR, SD or PD). PDTs demonstrated an 83% concordance in predicting patient therapy response, with 75% accuracy for predicting treatment sensitivity and 100% accuracy for predicting resistance. These findings suggest that FPO approaches are reproducible across different settings and their global implementation could benefit oncology patients. Supported by FAPESP-PIPE (2022/10646-4, 2023/1285-3), and INCT Model3D (CNPq). Citation Format: Luciana Harumi Osaki, Tiago Goss dos Santos, Stefano P. Clerici, Celso A. Mello, Tiago Felismino, Gabriel O. Santos, Rodrigo G. Taboada, Virgilio S. Silva, Samuel Aguiar Jr., Felipe Jose Coimbra, Adriane G. Pelosof, Angelo B Brito, Rubens Chojniack, Paula N.V.P. Barbosa, Denisse Esther Mallaupoma-Camarena, Adrhyann J.S. Portilho, Queila C. Dias, Isadora Rattes, Patricia Gama, Rachel S.P. Riechelmann, Vilma R. Martins. Expanding the geographic reach of functional precision oncology through prediction of therapy response with patient-derived tumoroids [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr B032.