L2 - Research models Flashcards
Cancer research models
Cell lines - patient’s cells taken from tumour
Organoids - 3D culture of cells
Xenografts - cell lines implanted in mouse
PDXs - patient-derived xenografts
Tumour-induced mouse models - GE mice
Zebrafish models - GE fish mimics
Omic-based models - Using real-world data
The features of a good cancer model
Predictive accuracy - do treatments translate
Relevance to human biology - tumour biology
Integrates heterogeneity - account for complexity
Scalability - how many conditions can you test
Reproducibility - i mean
Mechanical insight - how reductionist can it be
Cell lines pros
- Continuous and unlimited supply of cells
- Consistent genotype/phenotype
- Can be modified easily
- Cost-effective
- Can be grown in different conditions
- Excellent to study molecular interactions
- Automated process
- Maintain cells under controlled conditions
Cell lines cons
- Risk of genetic drift and mutation
- Artificial environment
- Possible contamination
- Lose relevant in-vivo characteristics
- Ethical concerns
- No gradients 3D or TME
- Homogenous cultures
Organoids pros
- Can be grown in different conditions
- Can be modified
- Continuous/unlimited growth
- Consistent genetic characteristics
- Cost-effectiveness
- Ability to maintain control
- Gradients and heterogenous
Organoids cons
- Risk of genetic drift
- Artificial environment
- Possible contamination
- Lose relevant in-vivo characteristics
- Ethical issues
- Less reproducible
- Harder to study mechanisms
- Homogenous cultures
Xenograft pros
- Closer in-vivo tumour biology
- Study tumour-host interactions
- Better drug development and testing
- Lots of cancer cell line variants
- Can study metastasis
Xenograft cons
- Limited generalisability
- No host immune defence
- Uses homogenous cell lines
- Ethical concerns
- Limited reproducibility
- Expensive
- Differences in tumour microenvironment (TME)
Tumour-induced models: two types
Genetic - tissue modified to express oncogenes
Spontaneous - uses cancer-causing agents to develop cancer
Tumour-induced models pros
- Closer in-vivo biology
- Study tumour-host interactions
- Potential in drug discovery and testing
- Controlled
- Ability to study tumour progression and metastasis
- Develops naturally with time and TME
Tumour-induced models cons
- Differences in TME
- Ethical issues
- Limited reproducibility
- Takes multiple months
- Not scalable
- High cost/expertise required
Zebrafish pros
- Rapid development
- Inexpensive
- Crossing models are rapid
- High-throughput screening
- Transparent embryos - easy for tumour visualisation
- Conservation of gene function across species
Zebrafish cons
- Differences in TME
- Ethical issues
- Limited reproducibility between species
- Trained expertise required
- Limited understanding of fish immune system and tumours
- Few drug discoveries
Omics pros
- High through-put analysis
- Ethical
- Increased data accuracy
- Ability to study complex biological mechanisms
- Non bias
- Integration of multiple layers of information
- Ease of data generation
Omics cons
- Problem of data interpretation and integration
- Basically no mechanical insight
- Limited functional analysis
- Large amounts of sample material
- Expensive
- Limited understanding of the cause-effect relationship between molecules-biological processes
- Can not stand alone
