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Genetically-engineered Mouse Models for Pancreatic Cancer
In vitro models lack the immune system and the microenvironment and are not representative of tumor heterogeneity. Since in vivo models can overcome the limitations of metastasis studies and allow the exploration of the complex crosstalk involved in metastasis and stages, they are key to investigating alternative and innovative therapies. Alfa Cytology is a leading global life sciences company. We are proud to offer genetically engineered mouse models for pancreatic cancer (PC) research.
Overview of Pancreatic Cancer Genetically Engineered Mouse Models (GEMMs)
Genetically engineered mouse models (GEMMs) transfer specific genes into mice via retrovirus by transgenic, knockout, and knock-in technologies. Pancreatic cancer genetically engineered mice are designed by inducing specific mutations in pancreatic cancer-associated oncogenes or tumor suppressor genes in the mouse genome. Transgenic mice overexpressing Kras mutant genes can mimic pancreatic tumorigenesis, most pancreatic cancer GEMMs currently in use are developed using the Kras proto-oncogene.
Fig. 1 Different strategies for creating transgenic mice. (Lampreht TU., et al.; 2018)
To date, several GEMMs can faithfully reproduce the genetic, molecular, histological, and clinical characteristics of human pancreatic cancer, including KC, KPC, KD, and KPCZ models. Among them, the KPC model containing mutations in KRAS and TP53, driven by the pdx1-Cre transgene, is the most well-studied. In the KPC model, similar to human pancreatic cancer, tumors develop spontaneously with dense connective tissue and a poor vascular system, thus maintaining the dynamics of the tumor microenvironment.
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Preclinical tumor studies are designed to mimic human disease in an animal setting, and the biggest challenge for researchers is the translatability of the results. The ideal preclinical tumor model requires not only a specific tumor subtype but also mimics the complex microenvironment required for tumorigenesis. As a result, the modeling time is difficult to control, time-consuming and costly. To meet experimental requirements in terms of quantity and quality, Alfa Cytology has launched a systematic animal model transgenic platform for pancreatic cancer research. Our platform is based on a series of technologies, such as conditional gene knockout technology and CRISPR-Cas9 technology.
- Conditional Gene Knockout Technology
This method can restrict gene modifications to a certain part or a certain developmental stage to enable precise control of the timing and space of mutated genes, thus allowing a more accurate study of gene function. We apply the most commonly used conditional gene knockout strategies, including the Cre/loxp recombinase and tet-on systems.
- CRISPR-Cas9 Technology
CRISPR-Cas9 technology allows for more precise genome editing. Using this method, we can generate syngeneic mouse models that recapitulate human pancreatic cancer features.
Applications of Our Pancreatic Cancer GEMMs
- Study the interactions between tumor and stromal cells, promoting the understanding of pancreatic cancer pathogenesis
- Study the disease progression from early stages of PanIN to primary and metastatic tumors
- Study the immune response in pancreatic cancer and test new immune-therapies
- Study the impact of microbiota composition and its effect on pancreatic cancer tumor development and patient survival
Pancreatic cancer GEMMs are similar in nature to human disease, and in particular, their metastatic pattern is most similar to that of human pancreatic cancer. These models can be applied to investigate early-stage pancreatic cancer tumor formation, allowing researchers to determine pancreatic cancer pathogenesis and treatment efficacy. We can provide a variety of effective and customized pancreatic cancer transgenic models for testing the effectiveness of drugs according to the specific needs of our clients. If you are interested in our services, please contact us for a professional, competitively priced solution that fits your needs.
References
- Kong, Kaiwen, et al. "Progress in animal models of pancreatic ductal adenocarcinoma." Journal of Cancer 11.6 (2020): 1555.
- Miquel, Maria, Shuman Zhang, and Christian Pilarsky. "Pre-clinical Models of Metastasis in Pancreatic Cancer." Frontiers in cell and developmental biology (2021): 2825.
