Preclinical cancer models Flashcards
In vitro or in vivo, which is best for drugs screens?
in vitro
In vitro or in vivo, which is best for therapy studies?
In vivo
Types of murine cancer model?
- synergic
- chemically induced
- viral induced
- tissue transplant
- GEMM
- xenotransplant
What is a spnotanoues murine model good for studying?
viral etiology
vertical transmission
cloning modifier loci
What is a chemically induced murine model good for studying?
big in Japan, not a fan
germ line or acquired mutants
What is a tissue transplant murine model good for studying?
- quick
- transplant
- confounded by irradiatio, integration site, in vitro selection.
What is a genetically engineered mice (GEM) model good for studying?
Tansgenic - tissue, time specific
Gene targeted - knock out/ on genes
What is a xenophobia graph?
- immunodeficient mouse
- insertion of cell line
- patient derived use actual tumour cells
Pros of viral induced cancer murine model?
- natural microenvironment
- intact immune system
- genetically homogenous
- transferable and repeatable
Cons of viral induced cancer murine model?
Not human cancer
Not human pharmacokinetics
Colonies can be huge
Pros of GEM models?
- natural microenvironment
- intact immune system
- genetically homogenous
- transferable and repeatable
Cons of GEM models?
Not human cancer
Not human pharmacokinetics
Colonies can be huge
Difficulty with large number off animals
Pros of Xeno models?
- Human cancer
- Easy to generate large numbers
- transferable and reproducible
Cons of Xeno models?
- Evolution/selective in plastic
- Foreign micro-enviorment
- Lack or immune system
- Not human pharmacokinetics
Pros of PDX models?
- Human, primary cancer
- easy to generate large numbers
Cons of PDX models?
- Expensive
- Not easily transferable
- lack of immune system
- Foreign micro-environment
- Not human pharmacokinetics
In vitro alternatives to murine models?
Patient-derived tumour organoids and mammosphrers
What is the best model for proving causation?
GEM (using CRISPR) as can start with primary cell. Cell lines are uncharacteristically abnormal.
What is the best model for observing disease progression?
GEM/ Xenogrpah as they have normal microenvironment
What is the best model for pre clinical therapeutics?
Spheroids, Organoids, GEMMs, Xeno-graph, PDX.
What is the best model for Gene/ pathway discovery?
In vitreo essay, high though put, NGS.
What is meant by a xenograph modal which is orthotic/ orthotropic?
Tumour placed into the site (of the mouse) where is arose from.
What relationship does tumour growth follow?
Gompertzian
How is labelling index defined?
proliferation marker stained cell / total cell count
