Abstract 4809: A novel microfluidic platform for PDAC organoid culture and drug screening

Abstract

Abstract Pancreatic Ductal Adenocarcinoma (PDAC), the most common pancreatic cancer type, will become the second leading cause of cancer-related deaths by 2030 with mortality rates of up to 93%. Current standard-of-care for patients with PDAC includes chemotherapeutic regimens and pancreatic cancer surgery. However, only 20% of the patients are eligible for surgery due to late diagnosis. Although chemotherapeutic regimens are the leading treatment to PDAC patients, these are still very limited and the development of resistance to treatment is often observed. PDAC tumors are characterized by high-density stroma and hypovascularization, therefore these present high interstitial pressure and hypoxia. These features potentially interfere with the efficiency of chemotherapeutic drugs and highlight the urgent need for novel PDAC screening platforms. Here, we describe the establishment of PDAC organoid cultures in the MIMETAS OrganoPlate®. The aim of this project was to determine the treatment response of PDAC organoids in mono-, and co-culture with pancreatic stellate cells (PSCs) under hypoxic and normoxic conditions. To recapitulate in-vivo like conditions, the 2-lane OrganoPlate® from MIMETAS was used to study organoid growth and sensitivity to treatment. Several standard of care (chemo-)therapeutics were tested on PDAC organoids embedded within an extracellular matrix in the Organoplate® 2-lane. These were exposed to chemotherapeutic treatments for 72h. PDAC organoids showed an overall better survival when grown in co-culture with PSCs. Interestingly, organoids grown in co-culture showed a higher survival rate under hypoxic conditions. In contrast, when grown in monoculture cell viability was higher or similar under normoxic conditions than in hypoxia for the different chemotherapeutics. The OrganoPlate® 2-lane provides an excellent platform for (co-) cultivation and high-throughput phenotypic drug screening of PDAC organoids, thereby potentially enabling the development of novel in-vivo like model systems for efficient patient stratification and drug discovery. Citation Format: Marlene Geyer, Daniel Schreyer, Lisa-Marie Gaul, Désiréé Goubert, Susanne Pfeffer, Christian Pilarsky, Karla S. Queiroz. A novel microfluidic platform for PDAC organoid culture and drug screening. [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 4809.