cancer models Flashcards
step wise model of cancer transformation
Mutation 1 - removes a negative regulator of cell cycle
Mutation 2 - activates a positive regulator of cell cycle
Mutation 3 - inhibits cell death
Additive effects of TME
Transformed cancer cells
what should a good cancer model have
- relevance to human biology
- predictive accuracy: do treatments translate
- scalability: how many conditions can you test
- reproducibility - should be easily reporducible
- integrates heterogenity - how complex is the system
- mechanic insight - how reductionist can it be
cell lines
cultured cancer cells, taken from a patient and grown in a lab
cell lines pros
- Continuous and unlimited supply of cells
- Consistent genetic and phenotype chatacteristics
- Ease of handling
- Can be modified easily and excellent Techniques to study molecular interactions
- Ability to maintain cells under controlled conditions
- Cost effectiveness
- Automated process
Can be grown in different conditions
cell lines negatives
- Risk of genetic drift and mutation
- Artificial environment
- Possible contamination issues
- Lose relevant in vivo characteristics
- Ethical concerns
- Homogenous cultures
- No gradients or 3D or TME
organoids
3D cultures of cells that mimic the structure and function of an organ
organoids pros
- continuous and unlimited supply of cells
- consistent genetic characteristics
- ease of handling
- can be modified easily
- ability to maintain cells under controlled conditions
- cost effectiveness
- gradients and heterogenous
-can be grown in different conditions
organoids negs
– risk of genetic drift and mutation
- artificial environment
- possible contamination issues
- lose relevant in vivo characteristics
- ethical concerns
- homogenous cultures
- less reproducible
- harder to study mechanisms
xenografts
use cells (cell lines) from patients implanted into a mouse
xenografts positives
- closer in vivo tumour biology
- study more tumour host interactions
- better drug discovery and testing
- lots of cancer cell line variants
- can study metastasis
xenografts negatives
- limited generalisability to humans
- no host immune system
- difference in TME
- ethical concerns
- limited reproducibility between animal models
- uses homogenous cell lines
- expensive
patient derived xenografts
use cells from a patients tumour that are implanted into a mouse, with the cells being maintained by serial passage in the mouse
tumour induced mouse models
genetically engineered mice models
- genetic models: tissue modified to express oncogenes
- spontaneous models: uses cancer causing agents to develop cancers
tumour induced mouse pros
- Close in vivo tumour biology
- Study tumour host interactions
- Potential in drug discovery and testing
- Controlled changes to genetic background
- Ability to study tumour progression and metastasis
- Develops naturally time and TME
tumour-induced mouse negs
- not scalable
- time takes months and months
- difference in TME
- ethical concerns
- limited reproducibility between different animal models
- high cost and technical expertise required