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Published on: October 4, 2022
Organ-Chip Models: Opportunities for Precision Medicine in Pancreatic Cancer
Muhammad R Haque1, Trevor H Rempert2, Taslim A Al-Hilal3
1Division of Digestive Diseases, Rush Center for Integrated Microbiome & Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, USA.
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.
Insights
Pancreatic cancer (PDAC) is deadly, with poor survival rates. New organoid and organ-on-a-chip models offer hope for personalized drug discovery by better mimicking the tumor microenvironment.
Area of Science:
- Oncology
- Biotechnology
- Cancer Research
Background:
- Pancreatic Ductal Adenocarcinoma (PDAC) has a dismal prognosis, with conventional chemotherapy often failing due to tumor heterogeneity and a suppressive tumor microenvironment (TME).
- The TME's fibro-inflammatory nature impedes drug delivery and efficacy, contributing to treatment resistance in pancreatic cancer.
- There is a critical need for advanced ex vivo models to develop personalized therapeutic strategies for PDAC.
Purpose of the Study:
- To review advances in organoid technology and multicellular platforms for modeling pancreatic cancer.
- To explore the potential of organ-on-a-chip approaches for recapitulating PDAC tumor complexity.
- To discuss the application of these models in preclinical drug screening and personalized treatment selection for PDAC.
Main Methods:
- Utilizing patient-derived three-dimensional (3D) organoids to model patient-specific cancerous epithelium.
- Incorporating tumor microenvironment (TME) components into organoid cultures for enhanced in vivo mimicry.
- Developing and analyzing organ-on-a-chip platforms to simulate complex cellular interactions in PDAC.
Main Results:
- Patient-derived organoids with TME components provide a more accurate representation of the in vivo tumor environment.
- Organ-on-a-chip technologies are advancing, offering sophisticated platforms for studying PDAC.
- These models show promise for understanding treatment response and resistance mechanisms.
Conclusions:
- Organoid and organ-on-a-chip technologies represent significant progress in modeling pancreatic cancer.
- These advanced platforms can facilitate the discovery of novel therapeutic regimens, including TME-targeting agents.
- The preclinical application of these models holds potential for individualized treatment selection in PDAC.
