Lecture 12: Animal Models of Cancer Flashcards
In vitro models
“Within a Glass” done in a test tube rather than living organism
In Vivo Models
“Within the living” process or experiment in a living organism
In Silica Models
“Within computers” computationally performed
Advantage of cell lines
Homogeneity and reproducibility in data
Limitations of cell cultures
Data generated from cellular systems does not truly phenocopy the intricate cellular interactions between different cell types, hormones, and extracellular matrices of an in vivo environment
GEMM Mice
Genetically Engineered Mouse Models of cancer to study the function of human genes in health and disease
MMTV-PyMT mouse model of breast cancer and lung metastasis
Mammary specific polyomavirus middle T antigen overexpression mouse model. Most commonly used genetically engineered mouse model (GEMM)
Cre-LoxP mouse model
-Deletion of any floxed
-Beta-Galactosidase marker/monitor using RosaLacZ gene
______ of ovarian cancer patients present with dysfunctional BRCA1/2
50%
Advantages of Patient-Derived xenograft (PDX) Models
- PDX-engrafted mice are a fast and cost-effective platform to simulate trials, evaluate drugs alone or in combination, and produce clinically predictive data
- Improve the predictability of human response to drugs later in clinical development
- Proof-of-concept testing of novel treatments & immunotherapies targeting T-cells
- PDX models mostly retain the principal histological and genetic characteristics of their donor tumor and remain stable across passages
- PDX models in mice can be generated from fresh primary or metastatic human cancer is extensively described in literature
PDX humanized mice
- Mouse engrafted with a human tumor known as PDX sometimes used as an avatar to guide customized patient care
- Scientists take a tumor from a patient and cut it into pieces for multiple mice
- Each fragment grows and can be divided into pieces for additional mice. Dozens of humanized mice are created with nearly identical tumors
- Scientists can treat different groups of PDX mice with alternative drugs to determine the best approach
Disadvantage of PDX Mice
Difficult to assess the relevance of tumors that occur in chemically treated animals in short-term studies
Phytoestrogens
Hormone-like compound that can be found in grain-based rodent diets that can affect onset of puberty and alter cancer risk
Devil Facial Tumors (DTV)
Spread by transfer of living cancer cells by biting and causing the appearance of tumors on the face or inside the mouth of affected devils. Clonally derived and is an allograft transmitted between devils by biting.
Origins of Devil Face Tumors
Schwann Cell origin in peripheral nerve sheath tumor
