Abstract 189: Developing a patient-derived organoid biobank, suitable for large scale drug screenings

Abstract

Abstract Conventional models for preclinical drug screening offer poor predictive value for patient response, causing high attrition rates of new agents in the clinic. HUB’s proprietary Patient-Derived Organoid (PDO) Technology enables long-term expansion of primary patient material to generate ‘mini organs in a dish’ that can be used as patient avatars, thus bringing every “patient in the lab®”. We present the world’s first NMIBC PDO biobank comprising 50 PDO models from transurethral resection of bladder (TURB) biopsies collected at three hospitals. Clinical and pathological characterization of the PDOs confirmed the representation in the biobank of a range of tumor stages and differentiation grades, as well as patient treatment and follow-up. The genomic analyses of PDOs revealed mutations in known BC driver genes and genomic instability, a hallmark of cancer. Finally, transcriptomic analyses confirmed gene expression profiles familiar to BC and characterized gene fusions. Next, we successfully screened the biobank on a panel of two reference compounds for the treatment of bladder cancer and seven candidate drugs, indicating potential new leads for further development of some of the compounds. The work presented here shows the feasibility of building PDO biobanks representing a specific patient population, suitable for improving the drug development pipeline for the next generation of cancer drugs. Citation Format: Lars-Eric Fielmich, Annemarie Buijs, Daniele Mori, Bas Viergever, Nihed Draoui, Anna Schepers, Mariana M. Costa e Silva, Mathijs Scholtus, Tokameh Mahmoudi, Tahlita Zuiverloon, Merel Derksen, Paul Gavine, Sylvia F. Boj, Richard Meijer, Onno Kranenburg, Janine Arts, Robert Vries. Developing a patient-derived organoid biobank, suitable for large scale drug screenings [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 189.