Novel 3-D In Vitro Models for Studying Pancreatic Cancer Drug Response and Resistance Webinar
March 28, 2024, at 12:00 PM ETAbstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a rapid mortality. Therapeutic resistance to chemotherapy is one of the main causes of treatment failure and ultimately death. Therefore, effective preclinical models are essential for providing a translational bridge between in vitro and in vivo studies to make clinically relevant discoveries. Patient-derived organoids (PDOs) are complex, self-organizing structures cultured from tumor cells embedded in a 3-D extracellular matrix. They display the self-renewal capacities, heterogeneity, preserved architecture, drug response, and genetic landscape of the original tumor—highly resembling the patient’s phenotypic characteristics. PDO culture requires a complex medium composition with specific niche growth factors and sophisticated techniques, which can be time-consuming and expensive to prepare. In this webinar, methodologies and experimental approaches to develop PDOs and isogenic primary cell lines as well as a method for recapitulating primary cell line cultures to organoids are described. The usefulness of cell line organoids (CLOs) as 3-D PDAC models is highlighted; these models maintain similar phenotype, in vitro architecture, and transcriptomic signatures as their matched PDOs. Additionally, a method for modeling drug resistance in PDOs is presented to identify clinically relevant resistance mechanisms to cytotoxic therapies. These models provide a manageable, expandable in vitro resource for multiple downstream applications and analyses.
Key takeaways
- Describe the role of preclinical systems focusing on organoids in modeling pancreatic cancer.
- Demonstrate that the 3-D CLO culture method can be used as an expandable, easy-to-scale-up, affordable, and less time-consuming research model.
- Highlight a methodology for the development and characterization of drug resistance using pancreatic cancer organoids.
Presenters
Naomi Walsh, MPH, PhD
Associate Professor, Life Sciences Institute, School of Biotechnology, Dublin City University
Dr. Naomi Walsh's current research is focused on developing organoid 3D cancer systems to model the genomic and transcriptomic landscape of rare and difficult to cure cancers such as pancreatic cancer to identify novel therapeutic combinations, and strategies to overcome drug resistance. Dr. Walsh completed a PhD in Cancer Research in Dublin City University (DCU) and Master of Public Health (MPH) in University College Dublin (UCD). She conducted her post-doctoral research in the Cancer Prevention Fellowship Program at the National Cancer Institute (NCI), USA.
