What is cancer?
A group of diseases all sharing similar characteristics
What are the characteristics that all cancers share?
They are all abnormal, uncontrolled growths of cells. They all show inappropriate proliferation, invasion, and metastasis
What are the characteristics of a benign tumour?
- Slow growth
- No metastasis
What are the characteristics of a malignant tumour?
- Rapid growth
- Potential for metastasis
What is the increase in incidence of cancer due to?
- Lifestyle changes
- Increased screening
What is carciogenesis?
The process of transformation of a 'normal' cell to a cancer cell
What are the stages in carciogenesis?
What happens in initiation?
A mutation in stem cells is acquried when they are exposed to a carcinogen, and you get unrepaired DNA damage
What happens in promotion?
There is induction of cell division, where the cancer starts from a single cell that has a selective advantage over other cells within the same tissue
How does promotion lead to progression?
Increased proliferation means increased mutations and therefore an increased advantage
What happens in progression?
What is there a potential for in transformation?
What can be produced in cancer evolution?
A drug resistant clinical tumour
What happens in cancer metastasis?
Spread of transformed cells
What stages of carciogenesis can be used to treat cancer?
Can enter at any stage to try and prevent disease
What does mutation lead to in colorectal carciogenesis?
Inactivation of the APC gene
What will an inactivation of the APC gene in colorectal carcinogenesis cause?
May cause a change in frequency in division, which leads to an increase in stem cells. This will develop over time into a cluster of APC-less cells with stem cell properties
What might the 'second hit' be in colorectal carcinogenesis?
Inactivation of Ras
What is the result of the inactivation of Ras in colorectal carcinogenesis?
Increased selective advantage
What might the third hit be in colorectal carcinogenesis?
Inactivation of p53
What happens after the third hit in colorectal carcinogenesis?
Increased growth, starts to form an adenoma
What does the forth hit in colorectal carcinogenesis lead to?
The rapid development of cancer
What extracellular/environmental factors can cause genes to mutate?
- Binding of ultimate carcinogens
- Ionising radiation/UV
- DNA translocation
What do ultimate carcinogens do?
Bind to DNA and alter the sequence
What effect does ionising radiation and UV have on DNA?
Causes strand breaks and cross links
When may DNA translocation cause mutations?
When it is translocation to transcriptionally active regions
What intracellular factors can cause mutations?
- Misinterpretation of code
- Polymerase slippage/base misalignment
- Ineffective repair
What can all mutations potentially affect?
What can act as initiating stimuli in carcinogenesis?
- Chemical carcinogens
- Oncogenic viruses
- UV light
- Oxygen free radicals
- Replication errors
When can oxygen free radicals act as an initiating stimuli for carcinogenesis?
When there is an imbalance between their production (which happens naturally) and their removal