cancer

• Cancer is a collection of diseases with the common feature of uncontrolled growth.
• Multiple causes contribute to cancer, with "life style" factors being a major influence.
• Cancer is not contagious, although some viral infections can predispose to disease.
• Some people are more susceptible to cancer than others, due to individual genetics.
• Several cellular changes are required to generate cancer.
• Cancer can occur in all cell types in the body, but epithelial cells are most prone to change.
• A kill signal in cancer is apoptosis.
• Cancer cells grow in a non-restrained fashion.
• Cancers can be restricted to the tissue of origin (local disease) or they invade other tissues.
• When cancer cells invade and colonise territories reserved for other cells, this is known as METASTASIS, which can occur via lymph node or a blood vessel.
• Once a cancer has metastasised, it is much more difficult to treat.
• All successful tumours share the Hallmarks of Cancer: Self-sufficiency in growth signals, Insensitivity to anti-growth signals, Limitless replicative potential, Evasion of apoptosis, Sustained angiogenesis, Tissue invasion and metastasis.
• Telomeres are chopped off each time the cell grows until it reaches a critical mass, the cell is at the end of its lifetime and die and is replaced.
• 1-4 means you have cancer.
• what are the examples of cause of cancer that are preventable?

  Smoking, excessive alcohol consumption, unhealthy diet, lack of physical activity, hormones
• what are the non-preventable causes of cancer?

  Genetics, aging, and environmental factors (such as UV light, radioactivity), viruses (e.g. hepatitis - liver cancer)
• how can tobacco cause cancer?

  • nicotine goes into bloodstream which goes to all organs in body
  • kidney cancer more prevalent to those who smoke
• how can diet cause cancer?

  unhealthy diet can increase some cancers as they come in contact with the food (e.g. the stomach) except for the lungs
• how could obesity lead to cancer?

  1. fat cells produce oestrogen - after the menopause, oestrogen made by fat cells can make cells multiply faster in the breasts and womb, increasing the risk of cancer
  2. excess fat can cause levels of insulin and other growth factors to rise, which can also tells cells to divide more rapidly
  3. where there is fat cells there are macrophages - cells in fat called macrophages (an inflammatory cell) release chemicals called cytokines, encouraging cells to divide (including cancer cells)
• whats one way alcohol can cause cancer?

  ethanol (alcohol) enters a stem cell and is converted to acetaldehyde by ADH enzyme.

  • acetaldehyde is a toxic chemical that if allowed to build up can cause:
  • chromosome rearrangements
  • mutations in DNA
  • (can be fixed by cells in body but if not = cancer)
  • damage can increase cancer risk - not definitive
• how can reproductive hormones cause cancer?

  there are tissues in the body that are hormone sensitive and so adding in exogenous hormones can have a slight increase in the risk of using exogenous hormones
• what are the 6 Hallmarks of Cancer?

  Self-sufficiency in growth signals, insensitivity to anti-growth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis.
• what does a cell have to have of the hallmarks of cancer to be classes as cancer?

  • self sufficiency in growth signals 
  • insensitivity to anti-growth signals 
  • limitless replicative potential 
  • evading apoptosis                                                                                         
• in normal cells, telomeres are chopped of each time the cell grows until it gets to a critical mass which means the cell it at the end of its lifetime and so dies and is replaced
• how do cancer cells become self-sufficient?

  
  

  • autocrine signalling
  • receptor over-expression
  • direct mutation of receptor
• normal cells need growth signals to proliferate and will not be able to grow ion the absence of these stimuli:

  but cancer cells are able to grow independantly

  • growth factors
  • components of the extracellular matrix (ECM)
  • cell-cell adhesion
• how can autocrine signalling cause cancer cells to become self-sufficient?

  • the cancer cells can produce excessive amounts of growth factors themselves and so become less dependant non external signals from neighbouring cells or surrounding tissue
  • this creates a self-sustaining loop where the cell stimulates its own growth and survival
  • e.g. PDGF in glioblastoma (most common form of malignant brain tumour)
• what is heterotypic signalling?

  refers to the communication between different cell types
• what is autocrine signalling?

  cell secretes a hormone/chemical messenger (growth factors) that bind to their own receptors leading to changes in the cell
• how does receptor over-expression cause cells to become self-sufficient?

  1. Increases sensitivity to growth factors - cancer cells become more sensitive to even low concentrations of the growth factors that promotes cell growth and division
  2. Over-expression can lead to autocrine stimulation where cancer cells produce their own growth factors and respond to these self-produced signals - it doesn’t rely on external signals
• examples of growth factors:

  • EGFR - made by stomach, brain + breast cells
  • HER2 - made by stomach, breast + lung cells
• how can direct mutation of receptor cause cells to become self-sufficient?

  • mutations can result in receptors that constantly activated or are hypersensitive to growth signals
  • allows ligand independent signalling - cellular signalling processes occurring in the absence of the normal binding of signalling molecule to its receptor
  • this is abnormal
  • e.g. EGFR: lungs
• How do cells become Insensitive to Anti-Growth Signals?

  when checkpoints in the cell cycle are ignored e.g. via mutations in the Rb protein (retinoblastoma protein)
• why do cells become insensitive to anti-growth signals if mutations occur in Rb protein?

  Because all signals for the checkpoints in the cell cycle are sensed by the Rb protein
• resistance to growth inhibitors - cancer cells can become resistance to the inhibitory effects of certain molecules that normally.suppress cell growth
• what are the checkpoints during the cell cycle?

  Checkpoint during G1 - cell decides whether to proliferate or not

  CP during G1/S - looks for DNA damage and tries to fix themselves before progressing with the cell cycle - managed by p53 protein (a tumour suppressor)

  CP during G2 - cell access whether the chromosome replication has been successful - continue or not?

  After metaphase - determines whether all the sites chromatids are correctly attached to the spindle fibres
• what is apoptosis?

  programmed cell death

  • maintains tissue homeostasis by eliminating damaged, unwanted or potentially harmful cells
• evading apoptosis allows cancer cells to have the ability to increase in number = cell division>cell death
• how do cancer cells evade apoptosis?

  p53 is a tumour suppressor and is described as the ‘guardian of the genome’ so when mutated it means cells do not die when they should
• whats the function of p53?

  • if DNA damage is identified it will halt the cell cycle (G1/S)
  • it activates DNA repair proteins when DNA has sustained damage
  • it initiates apoptosis if the damage can’t be repaired