Cancer Flashcards
When is a tumour said to be malignant?
When primary tumour invades surrounding tissue
How do cancer cells spread?
Via blood or lymph
True or False:
Great majority of cancers are secondary to external factors.
True
How does cancer develop?
The body has a series of effective intrinsic defences to fight off
cancer development but eventually the defence mechanisms are overcome step by step
What are the steps of cancer formation?
Initiation (mutation in a single cell)
Promotion (initiated cell proliferates»_space; normal cells -> clonal expansion -> additional mutations)
Malignant conversion -> critical irriversible mutation
Progression -> Malignant cells continue to mutate
What are some environmental agents that can trigger tumorigenesis?
Tobacco smoke >15500cancers/yr in Australia
UV irradiation > 7200/yr
Poor diet > 7000/yr
Infections > 3400/yr
Alcohol > 3200/yr
Why are many mutations needed for cancer to develop?
• Tumour cells accumulate a number of mutations
(capabilities) to evade normal checks and balances on
cell growth, division, death & movement
• Mutations occur in a limited number of key genes
• At least 8 new capabilities (steps) are required
What are the 6 capabilities of cancer cells?
Able to sustain own growth (mediated by own growth signals)
Can’t be inhibited by growth inhibitory signals
Can evade apoptosis
Can proliferate indefinitely without issues
Can promote blood vessel growth
Can spread away from primary tumour
What do growth factors do?
They bind to GF-R receptors or Receptor Tyrosine Kinases to convert EC to IC.
They instruct cells to proliferate
How do tumours become self-sufficient for growth?
Cells start producing GF and responding to their own GF with GFR overexpression.
Mutational activation of GF-R
Constitutive activation of intracellular signalling:
Ras/Raf/MAPK proliferation pathway
P13K/Akt growth/survival pathway
How do tumours become insensitive to growth inhibition?
Many familial cancers are caused by inheritence of a mutated TSG allele.
Prototypical TSG - retinoblastoma (Rb) is most commonly disrupted in human tumours. This pathway responds to most extracellular anti-proliferative pathways
What is a TSG gene?
Tumour Suppressing Gene
How do TSGs suppress proliferation?
TSGs suppress proliferation by either:
• ↓ proliferation
• ↑ apoptosis, (↑ cell loss)
How do tumours avoid apoptosis?
Hormone receptor (ER & AR) expression ↑ -
survival signal
• Anti-apoptotic protein expression↑ -
B cell lymphomas often show upregulation of Bcl-2
Mechanisms of Apoptosis
Evasion in Tumours
• Most common pathway affected - mutations of the p53
tumour suppressor gene:
• p53 is a key DNA damage sensor - activates apoptosis in cells with severe DNA damage or metabolic problems
• Dominant negative (interfere with WT protein) or
inactivating p53 mutations are seen in ~50% of tumours
How do tumours prevent telomere shortening from inactivating their growth?
85 - 90% of tumours upregulate telomerase
