Lecture 1 Flashcards
Hallmarks of Cancer
- Evading Growth Suppressors
- Activating invasion and metastasis
- Avoiding immune Destruction
- Enabling replicative immortality
- Genome Instability and mutation
- Inducing Angiogenesis
- Resisting cell death
- Sustaining proliferative signalling
2 underpinning Charateristics
- Ability to avoid immune destruction and genomic instability
- Drive all the other hall marks
Why is cancer and “evolutionary disease”?
Cells evolve and compete with other cells- evolution of the “nastiest”
Major risk factor
AGE
Cancer prevalence/risk
Increase in cancer because more old people around to get it
Different risk and dependent on countries
Log incidence vs log age
Linear
Prostate, Colon and breast env or genetics ?
Environmental - Migration japan to hawaii
- major disease risk environmental
P(C1)
The probability of a change associated with cancer
- The chance that will have happened goes up with age.
If severall changes needed (n) before a tumour (T) develops what is the probability of all relevant changes:
LogP(T) = nlogA + constant
Log incidence
Log incidence = nLog A + constant
- slope n is the number of changes to produce a tumour
If P(T)=
Tumour incidence
Whatever the changes, what is the number that has to occur ??
6
susceptibility
Can run in familial genetics e.g -RB -Breast -Colon -wilms tumour- kidney Implies- tumour suppressor genes
What did percival pott establish ?.
Chimney Sweeps act - Scrotal cancer high incidence
What did John Hill do ?
identified correlation between snuff and nasopharyngeal cancer
Richard Doll
Father of cancer epidemiology - increase in smoking/ increase in lung cancer death
- lung cancer rareunless you smoke
1915- Yamagiwa first experimental model for inducing cancer
- Organic extraction of coal tar
- Inject in rabbits ears
- Induce carcinomas in ear
- Show you can deliberately induce cancer
Benzopyrene – cause cancer
Mutagenesis theory of cancer 1950s
- X rays could induce cancer
- Chicken virus
- Coal tar -Benzopyrene
Chemical/ physical/viral
Mouse cancer model – 2 kinds of mouse model
Oncomouse genetically engineered – look at endogenous cancers in that organism
Xenograft model of human cancer – immune- compromised mouse and inject cancerous cells develop tumours derived from human cancer cells
- Good for human drug development
- Demonstrate efficacy in xenograft model
- Mice get cancer but dont live as long as humans
