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Updated: Jul 6, 2025
Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
Published on: June 20, 2015
Breaking the stromal barrier in pancreatic cancer: Advances and challenges
Mohana Chakkera1, Jeremy B Foote2, Batoul Farran3
1Department of Hematology and Oncology, Heersink School of Medicine, University of Alabama, Birmingham, AL 35233, USA.
Abstract:
Pancreatic cancer (PC) remains a leading cause of mortality worldwide due to the absence of early detection methods and the low success rates of traditional therapeutic strategies. Drug resistance in PC is driven by its desmoplastic stroma, which creates a barrier that shields cancer niches and prevents the penetration of drugs. The PC stroma comprises heterogeneous cellular populations and non-cellular components involved in aberrant ECM deposition, immunosuppression, and drug resistance. These components can influence PC development through intricate and complex crosstalk with the PC cells. Understanding how stromal components and cells interact with and influence the invasiveness and refractoriness of PC cells is thus a prerequisite for developing successful stroma-modulating strategies capable of remodeling the PC stroma to alleviate drug resistance and enhance therapeutic outcomes. In this review, we explore how non-cellular and cellular stromal components, including cancer-associated fibroblasts and tumor-associated macrophages, contribute to the immunosuppressive and tumor-promoting effects of the stroma. We also examine the signaling pathways underlying their activation, tumorigenic effects, and interactions with PC cells. Finally, we discuss recent pre-clinical and clinical work aimed at developing and testing novel stroma-modulating agents to alleviate drug resistance and improve therapeutic outcomes in PC.
Insights
Pancreatic cancer drug resistance is driven by its dense stroma. Targeting stromal components offers a promising strategy to improve treatment outcomes for this deadly disease.
Area of Science:
- Oncology
- Cancer Biology
- Immunology
Background:
- Pancreatic cancer (PC) has high mortality due to late detection and ineffective therapies.
- The tumor stroma, a complex mix of cells and extracellular matrix, promotes drug resistance in PC.
- Understanding stroma-PC cell interactions is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To review the role of non-cellular and cellular stromal components in pancreatic cancer.
- To examine signaling pathways involved in stroma activation and PC cell interaction.
- To discuss novel stroma-modulating agents for improving PC treatment.
Main Methods:
- Literature review of preclinical and clinical studies.
- Analysis of the cellular and non-cellular components of the pancreatic cancer stroma.
- Examination of signaling pathways and crosstalk between stromal cells and PC cells.
Main Results:
- Stromal components, including cancer-associated fibroblasts and tumor-associated macrophages, create an immunosuppressive and tumor-promoting microenvironment.
- Aberrant extracellular matrix deposition by the stroma hinders drug penetration.
- Complex crosstalk between stromal elements and PC cells drives invasiveness and refractoriness to therapy.
Conclusions:
- The pancreatic cancer stroma significantly contributes to therapeutic resistance.
- Targeting stromal components and their interactions with cancer cells is a viable strategy to overcome drug resistance.
- Further research and development of stroma-modulating agents are essential for improving patient outcomes in pancreatic cancer.
