Summary Nutrition and Cancer (HNH-37806)

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