Hallmarks of cancer
Sustaining proliferative signalling
- Chronic proliferation growth factors
- Increased synthesis of growth factors by tumour cells
- Increased synthesis of growth factors by neighbouring cells
- Increased receptors at cell surface
- Structural alterations receptors increases response
- Activation downstream pathway
- Vb: epidermal growth factor(EGF)
Evading growth suppressors
- Escape stop signal
- Proliferation suppressors- tumour suppressor genes
- Proliferation senescence, apoptosis
- Vb: retinoblastoma-associated protein
Resisting cell death
- Inhibited apoptosis and autophagy
- Increased necrosis release of cell content, proinflammatory signals
- Vb: tumour protein 53= damage sensor, due mutation damaged DNA is not seen
Enabling replicative immortality- unlimited replication
- Immortilization
- Extending telomeres
- Alive
- Telomerase high
Inducing angiogenesis
- cells need nutrients and oxygen
- angiogenesis: new blood vessels
- support neoplastic growth
- early stage event
- target for therapy
- vb: vascular endothelial growth factor(VEGF)
- hypoxia and oncogenic stimuli
- VEGF increased
- Allow metastasis
Activating invasion and metastasis
- Spread of cancer cells via blood or lymphatic vessels
- Distant organs
- Multistep process
- Each tumour own preferences and latency time
- Prostate bone
- Breast lung, liver, brain
- Melanoma lung, liver, brain
, - Colorectal liver, lung
- Lung brain, bone, adrenal gland and liver
- Invasion-metastasis cascade
Primary tumor formation
Local invasion
Intravasation
Survival in circulation
Arrest at distant organ site
Extravasation
Micrometastasis formation
Metastatic colonization
Clinically detectable macroscopic metastases
Epithelial-to-mesenchymal transition
- Epithelial cells mesenchymal cells
- Adherence, motility, migration, invasion
- Reverse process of EMT=MET
- Mesenchymal cells lose orientated so they can easier become lose, get into the bloodstream
and are transported to another part of the body(EMT)
- MET: the cells become strictly oriented again, so they can form a structure(tumour) on the
distinct location
Genome instability and mutation(enabling)
- Alterations on the genomes
- Oncogenes are mutated genes whose presence can stimulate the development of cancer,
one mutation leads to accelerated cell division
- Tumour suppressor genes are normal genes whose absence can lead to cancer, one mutation
means susceptible carrier, two mutations leads to cancer stop signal does not work
- Passenger mutation
Mutation has no effect on neoplastic process
Number of mutations correlates with age(during normal growth)
Predominantly in self-renewing tissues(fast proliferating)
- Drivers mutation
Mutation conferring a selective growth advantage for the cell
Tumour-promoting inflammation(enabling)
- Infiltration of immune cells
- Supplying bioactive molecules to microenvironment
- Tumour inhibition as well a tumour promotion
Deregulating cellular energetics(emerging)
- Metabolic reprogramming for energy requirements
Avoiding immune destruction(ermerging)
- Escape immune surveillance
- T lymphocytes and NK cells
- Mechanisms are emerging
Sustaining proliferative signalling
- Chronic proliferation growth factors
- Increased synthesis of growth factors by tumour cells
- Increased synthesis of growth factors by neighbouring cells
- Increased receptors at cell surface
- Structural alterations receptors increases response
- Activation downstream pathway
- Vb: epidermal growth factor(EGF)
Evading growth suppressors
- Escape stop signal
- Proliferation suppressors- tumour suppressor genes
- Proliferation senescence, apoptosis
- Vb: retinoblastoma-associated protein
Resisting cell death
- Inhibited apoptosis and autophagy
- Increased necrosis release of cell content, proinflammatory signals
- Vb: tumour protein 53= damage sensor, due mutation damaged DNA is not seen
Enabling replicative immortality- unlimited replication
- Immortilization
- Extending telomeres
- Alive
- Telomerase high
Inducing angiogenesis
- cells need nutrients and oxygen
- angiogenesis: new blood vessels
- support neoplastic growth
- early stage event
- target for therapy
- vb: vascular endothelial growth factor(VEGF)
- hypoxia and oncogenic stimuli
- VEGF increased
- Allow metastasis
Activating invasion and metastasis
- Spread of cancer cells via blood or lymphatic vessels
- Distant organs
- Multistep process
- Each tumour own preferences and latency time
- Prostate bone
- Breast lung, liver, brain
- Melanoma lung, liver, brain
, - Colorectal liver, lung
- Lung brain, bone, adrenal gland and liver
- Invasion-metastasis cascade
Primary tumor formation
Local invasion
Intravasation
Survival in circulation
Arrest at distant organ site
Extravasation
Micrometastasis formation
Metastatic colonization
Clinically detectable macroscopic metastases
Epithelial-to-mesenchymal transition
- Epithelial cells mesenchymal cells
- Adherence, motility, migration, invasion
- Reverse process of EMT=MET
- Mesenchymal cells lose orientated so they can easier become lose, get into the bloodstream
and are transported to another part of the body(EMT)
- MET: the cells become strictly oriented again, so they can form a structure(tumour) on the
distinct location
Genome instability and mutation(enabling)
- Alterations on the genomes
- Oncogenes are mutated genes whose presence can stimulate the development of cancer,
one mutation leads to accelerated cell division
- Tumour suppressor genes are normal genes whose absence can lead to cancer, one mutation
means susceptible carrier, two mutations leads to cancer stop signal does not work
- Passenger mutation
Mutation has no effect on neoplastic process
Number of mutations correlates with age(during normal growth)
Predominantly in self-renewing tissues(fast proliferating)
- Drivers mutation
Mutation conferring a selective growth advantage for the cell
Tumour-promoting inflammation(enabling)
- Infiltration of immune cells
- Supplying bioactive molecules to microenvironment
- Tumour inhibition as well a tumour promotion
Deregulating cellular energetics(emerging)
- Metabolic reprogramming for energy requirements
Avoiding immune destruction(ermerging)
- Escape immune surveillance
- T lymphocytes and NK cells
- Mechanisms are emerging
