Abstract
Pancreatic duct adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related deaths in the next few years. Unfortunately, the development of novel therapies for PDAC has been challenged by a uniquely complex tumor microenvironment. The development of in vitro cancer organoids in recent years has demonstrated potential to increase therapies for patients with PDAC. Organoids have been established from PDAC murine and human tissues and they are representative of the primary tumor. Further, organoids have been shown beneficial in studies of molecular mechanisms and drug sensitivity testing. This review will cover the use of organoids to study PDAC development, invasiveness, and therapeutic resistance in the context of the tumor microenvironment, which is characterized by a dense desmoplastic reaction, hindered immune activity, and pro-tumor metabolic signaling. We describe investigations utilizing organoids to characterize the tumor microenvironment and also describe their limitations. Overall, organoids have great potential to serve as a versatile model of drug response and may be used to increase available therapies and improve survival for patients with PDAC.
Highlights
Pancreatic duct adenocarcinoma (PDAC) is a devastating disease with a 5-year survival in the US of just 10% and a projection to become one of the top leading causes of cancer-related deaths by 2030 [1,2]
Pancreatic cancer is characterized by rapid growth and invasiveness, and therapeutic targeting is complicated by multiple facets of the tumor microenvironment, including desmoplastic reaction, immunosuppression, and complex metabolic interactions [3,4,5]
This review focuses on the use of PDAC organoids to study components of the tumor microenvironment important for PDAC survival, including stromal reinforcement, immune evasion, and the rapid metabolic breakdown of drugs
Summary
Pancreatic duct adenocarcinoma (PDAC) is a devastating disease with a 5-year survival in the US of just 10% and a projection to become one of the top leading causes of cancer-related deaths by 2030 [1,2]. In vivo models; they present an attractive alternative theinteractions, rapid study of require 4–8 months to develop before sufficient material is generated for drug sensitivity testing [9–. The methods for establishing PDAC organoids from biopsy specimens and surgical tissues have attractive alternative for the rapid study of molecular interactions and drug response. Organoids serve as a valuable model for translational cancer research They are extremely versatile and may be manipulated to study important factors contributing to PDAC growth and invasiveness. They are accurate models of drug sensitivity and some groups are currently incorporating organoids for testing drugs in human clinical trials (NCT03544255, NCT03500068). This review focuses on the use of PDAC organoids to study components of the tumor microenvironment important for PDAC survival, including stromal reinforcement, immune evasion, and the rapid metabolic breakdown of drugs
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