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Updated: Dec 21, 2025
Organotypic Slice Cultures as Preclinical Models of Tumor Microenvironment in Primary Pancreatic Cancer and Metastasis
Published on: June 22, 2021
The tumour microenvironment in pancreatic cancer - clinical challenges and opportunities
Won Jin Ho1, Elizabeth M Jaffee1, Lei Zheng2
1Sidney Kimmel Comprehensive Cancer Center, The Skip Viragh Pancreatic Cancer Center for Clinical Research and Care, and The Bloomberg-Kimmel Institute for Immunotherapy at Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Abstract:
Metastatic pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid tumours despite the use of multi-agent conventional chemotherapy regimens. Such poor outcomes have fuelled ongoing efforts to exploit the tumour microenvironment (TME) for therapy, but strategies aimed at deconstructing the surrounding desmoplastic stroma and targeting the immunosuppressive pathways have largely failed. In fact, evidence has now shown that the stroma is multi-faceted, which illustrates the complexity of exploring features of the TME as isolated targets. In this Review, we describe ways in which the PDAC microenvironment has been targeted and note the current understanding of the clinical outcomes that have unexpectedly contradicted preclinical observations. We also consider the more sophisticated therapeutic strategies under active investigation - multi-modal treatment approaches and exploitation of biologically integrated targets - which aim to remodel the TME against PDAC.
Insights
Metastatic pancreatic ductal adenocarcinoma (PDAC) remains lethal despite chemotherapy. Novel therapies targeting the complex tumor microenvironment (TME) are crucial for improving patient outcomes.
Area of Science:
- Oncology
- Cancer Biology
- Immunotherapy
Background:
- Metastatic pancreatic ductal adenocarcinoma (PDAC) presents a significant therapeutic challenge with poor survival rates.
- Conventional chemotherapy has limited efficacy against advanced PDAC.
- The tumor microenvironment (TME), including the desmoplastic stroma and immunosuppressive pathways, is a key factor in PDAC progression and treatment resistance.
Purpose of the Study:
- To review current therapeutic strategies targeting the PDAC tumor microenvironment (TME).
- To analyze the discrepancies between preclinical findings and clinical outcomes of TME-targeted therapies.
- To explore advanced therapeutic approaches for remodeling the TME against PDAC.
Main Methods:
- Comprehensive literature review of studies investigating TME-targeted therapies for PDAC.
- Analysis of clinical trial data and outcomes.
- Discussion of emerging multi-modal treatment strategies and biologically integrated targets.
Main Results:
- Previous strategies targeting isolated TME components, such as stroma deconstruction and immunosuppression, have largely failed to improve clinical outcomes.
- Preclinical observations regarding TME-targeted therapies have often contradicted actual clinical results.
- The multi-faceted nature of the PDAC TME complicates the targeting of individual components.
Conclusions:
- Targeting the PDAC TME requires sophisticated, multi-modal approaches rather than single-agent strategies.
- Future research should focus on understanding the complex interactions within the TME to develop effective therapies.
- Remodeling the TME against PDAC holds promise for improving treatment efficacy and patient survival.
