Cancer model of disease Flashcards
What is cancer
increased cell proliferation and deceased cell death
Describe in vitro models
Cancer cell lines grow indefinitely, resilient, multiply quickly
Adherent or non-adherent (floating)
Describe combination studies
If new drugs work well with others
Chou-Talalay method -additive, synergistic, antagonistic?
What is co-culture
Direct mixing of cells
Boyden chambers
Describe 3D spheroids
Better mimic microenvironment
Edge and centre proliferate at different rate, metabolism, matrix
Hypoxic and acidic centres
Difficult and variable
What can vivo models replicate
Can model primary and metastatic tumours
- Tumour type
- tumour genetics
- tumour location
- microenvironment
- vasculature
- Immune system
What can in vivo models predict
Bioavailability (ADME)
Efficacy
Resistance development
Toxicology
Describe mouse models for cancer (in vivo)
Nude inbred mice with xenografts injected subcutaneously
Reduced immune system (lack thymus)
East to use
Can monitor tumour growth and easily extract
What are the disadvantages of a mouse model
Doesn’t provide a complete picture
- no immune system means different tumour development
- Incomplete stroma (difficult to test agents targeting human stroma)
How do you make mouse models more relevant
Syngeneic mouse models - intact immune system and tumour derived from same genetic background as mouse strain
Orthotopic mouse models - Place tumour in organ which it would have developed (better representation)
What are the
What are the
Describe conditional models
K-ras mutations in lung cancer - models of spontaneous develop lung tumours but die early from respiratory failure so can’t study progression
Add mutation with removable transcriptional termination element. Can be removed by virus and mutation is switched on
What do you need to consider in in vivo testing
Cost
Convenience
Throughput against biological relevance
