期刊
DISEASE MODELS & MECHANISMS
卷 8, 期 10, 页码 1185-1200出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dmm.021055
关键词
Co-clinical trials; Preclinical mouse models; Pancreatic ductal adenocarcinoma; PDAC; Drug discovery; Drug development
资金
- Cancer Research UK
- Cancer Research UK Glasgow Centre
- BSU facilities at the Cancer Research UK Beatson Institute
- Cancer Research UK Cambridge Institute grant [C14303/A17197]
- Cambridge Cancer Centre
- Cancer Research UK [15678] Funding Source: researchfish
- Cancer Research UK
- Versus Arthritis [21139] Funding Source: researchfish
- Cancer Research UK
- Versus Arthritis [20409] Funding Source: researchfish
Pancreatic ductal adenocarcinoma is the most common form of pancreatic tumour, with a very limited survival rate and currently no available disease-modifying treatments. Despite recent advances in the production of genetically engineered mouse models (GEMMs), the development of new therapies for pancreatic cancer is still hampered by a lack of reliable and predictive preclinical animal models for this disease. Preclinical models are vitally important for assessing therapies in the first stages of the drug development pipeline, prior to their transition to the clinical arena. GEMMs carry mutations in genes that are associated with specific human diseases and they can thus accurately mimic the genetic, phenotypic and physiological aspects of human pathologies. Here, we discuss different GEMMs of human pancreatic cancer, with a focus on the Lox-Stop-Lox (LSL)-Kras(G12D); LSL-Trp53(R172H); Pdx1-cre (KPC) model, one of the most widely used preclinical models for this disease. We describe its application in preclinical research, highlighting its advantages and disadvantages, its potential for predicting clinical outcomes in humans and the factors that can affect such outcomes, and, finally, future developments that could advance the discovery of new therapies for pancreatic cancer.
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