Evolutionary model of resistance
- Stochastic birth/death process:
- within any time interval, the following can happen:
- cell division
- cell death
- nothing happens
- Mutation might happen during cell division (mutation rate u)
- Multiple mutations might confer resistance to the same therapy
- evolve according to the same process as above
- Questions model can answer:
- prob of de novo resistance
- expected size of resistaant pop.
- diversity of resistant pop (number of celltypes, relative pop sizes)
- prob of resistance development for treatment schedules
- Treatment schedule models birth and death rates of sensitive and resistant cell populations
Resistance in chronic myeloid leukemia (CML):
- Gleevec (imatinib) inhibits activity of oncoprotein BCR-ABL
- point mutation in kinase domain confer resistance to this drug
- Prior to treatment: wide variety of cell types in population
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