Organ-Chip Models: Opportunities for Precision Medicine in Pancreatic Cancer

Abstract

Simple Summary Among all types of cancer, Pancreatic Ductal Adenocarcinoma (PDAC) has one of the lowest survival rates, partly due to the failure of current chemotherapeutics. This treatment failure can be attributed to the complicated nature of the tumor microenvironment, where the rich fibro-inflammatory responses can hinder drug delivery and efficacy at the tumor site. Moreover, the high molecular variations in PDAC create a large heterogeneity in the tumor microenvironment among patients. Current in vivo and in vitro options for drug testing are mostly ineffective in recapitulating the complex cellular interactions and individual variations in the PDAC tumor microenvironment, and as a result, they fail to provide appropriate models for individualized drug screening. Organ-on-a-chip technology combined with patient-derived organoids may provide the opportunity for developing personalized treatment options in PDAC. Abstract Pancreatic Ductal Adenocarcinoma (PDAC) is an expeditiously fatal malignancy with a five-year survival rate of 6–8%. Conventional chemotherapeutics fail in many cases due to inadequate primary response and rapidly developing resistance. This treatment failure is particularly challenging in pancreatic cancer because of the high molecular heterogeneity across tumors. Additionally, a rich fibro-inflammatory component within the tumor microenvironment (TME) limits the delivery and effectiveness of anticancer drugs, further contributing to the lack of response or developing resistance to conventional approaches in this cancer. As a result, there is an urgent need to model pancreatic cancer ex vivo to discover effective drug regimens, including those targeting the components of the TME on an individualized basis. Patient-derived three-dimensional (3D) organoid technology has provided a unique opportunity to study patient-specific cancerous epithelium. Patient-derived organoids cultured with the TME components can more accurately reflect the in vivo tumor environment. Here we present the advances in organoid technology and multicellular platforms that could allow for the development of “organ-on-a-chip” approaches to recapitulate the complex cellular interactions in PDAC tumors. We highlight the current advances of the organ-on-a-chip-based cancer models and discuss their potential for the preclinical selection of individualized treatment in PDAC.