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Experimental models of pancreas cancer: what has been the impact for precision medicine?
Vasiliki Pantazopoulou1,2, Casie S Kubota1, Satoshi Ogawa1
1Salk Institute for Biological Studies, San Diego, California, USA.
Abstract:
Pancreatic cancer has a 5-year survival rate of approximately 13% and is projected to become the second-leading cause of cancer-related deaths by 2040. Despite advances in preclinical research, clinical translation remains challenging, and combination chemotherapy remains the standard of care. The intrinsic heterogeneity of pancreas cancer underscores the potential of precision medicine approaches to improve patient outcomes. However, clinical implementation faces substantial challenges, including patient performance status, metastatic disease at diagnosis, intrinsic drug resistance, and a highly complex tumor microenvironment. Emerging targeted therapies, such as RAS inhibitors, offer promise for personalized treatment. These developments have prompted precision medicine-focused clinical trials using molecular subtyping for patient stratification. Effective development of precision medicine therapies depends heavily on robust preclinical models capable of accurately recapitulating the complexities of the pancreatic tumor microenvironment. Two-dimensional, air-liquid interface, and patient-derived organoid cultures combined with in vivo genetically engineered mouse models and patient-derived xenografts represent valuable experimental systems. This Review critically examines the strengths and limitations of these experimental model systems. We highlight their relevance and utility for advancing precision medicine strategies in pancreas cancer.
Insights
Pancreatic cancer research faces challenges in clinical translation. This review examines preclinical models for advancing precision medicine in pancreatic cancer treatment.
Area of Science:
- Oncology
- Translational Research
- Cancer Biology
Background:
- Pancreatic cancer has a low 5-year survival rate and is a leading cause of cancer deaths.
- Current treatments rely on combination chemotherapy, with limited success due to tumor heterogeneity and microenvironment complexity.
- Precision medicine offers potential but faces clinical implementation hurdles.
Purpose of the Study:
- To critically examine the strengths and limitations of various preclinical models for pancreatic cancer.
- To highlight the relevance of these models for advancing precision medicine strategies.
- To assess the utility of experimental systems in recapitulating the pancreatic tumor microenvironment.
Main Methods:
- Review of existing literature on preclinical models for pancreatic cancer.
- Analysis of 2D cultures, air-liquid interface cultures, organoid cultures, genetically engineered mouse models, and patient-derived xenografts.
- Evaluation of model systems' ability to mimic the pancreatic tumor microenvironment.
Main Results:
- Preclinical models like organoids and xenografts show promise in replicating pancreatic cancer complexity.
- Different models possess unique strengths and limitations for studying drug resistance and tumor microenvironment.
- Emerging targeted therapies, such as RAS inhibitors, are being investigated in precision medicine trials.
Conclusions:
- Robust preclinical models are essential for the effective development of precision medicine therapies for pancreatic cancer.
- Understanding the tumor microenvironment is crucial for improving treatment outcomes.
- Continued evaluation and refinement of experimental systems are needed to accelerate clinical translation.
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