Introduction to Cancer 2 Flashcards
What are the 6 hallmarks of cancer ?
1) Sustaining proliferative signalling
2) Evading growth suppressors= ignore the other cells and continue to grow
3) Activating invasion and metastasis= metastasis complicates the function of the organ
4) Enabling replicative immortality= ignoring any mechanisms initiating death
5) Inducing angiogenesis= fundamental for tumours to grow
6) Resisting cell death
What is cancer and what does it require?
COLLECTION of related diseases- tumours go through many of the same processes
They can start from almost any cell type
They require multiple mutations and undergo uncontrolled cell division
It is a step-wise process and can damage surrouding organs which is a key issue of the disease. They can also sometime metastasise.
In breast tissue what is the most common cell type to develop cancer?
the epithelial cells within the ducts
Where else in breast tissue can tumours occur ?
Within the lobules and stroma
Why is breast tissue prone to tumourogenesis?
because it is very sensitive to hormonal changes
What is the difference between ductal carcinoma and invasive ductal carcinoma?
ductal carcinoma= it is cancer but it is retained within the basement membrane and an operation is relatively easy because the tumour can be removed
invasive ductal carcinoma= the tumour cells break through the basement membrane and this allows them to metastasise.
What are the different ways of classifying cancers?
Malignant/benign= any malignant tumour left from surgery will continue to grow leading to relapse
Pathology/histological subtype
- receptor status
Grade= level of differentiation- the more undifferentiated the worse the tumour is
Stage
- size
- spread= confined or spreading throughout the body
Molecular= gene expression- the level of improvement for treatment based on this is limited
What are the receptor status’ in breast cancer?
It is one of the most important ways to classify breast cancer
estrogen receptor= use hormone eblation therapy such as tamoxifen or aromatase inhibitors to block the production of estrogen
progesterone receptors are also important
What is the link between Her2/ErbB2 in breast cancer?
this is a signalling molecule which can change its gene transcription
Perceptin- monoclonal antibody that stops this molecule being activated by its ligand
What happens to breast cancer patients that are triple negative?
They dont demonstrate any pathological/histological references, so they are given a horrible concoction of cytotoxic chemotherapeutic drugs
What is a mutation ?
it is a changes in DNA- causes changes it how genes behave and their physiology
Why are mutations very important ?
They are essential for evolution- they are the raw material of genetic variation
What are the types of bases ?
Pyrimidines= cytosine, thymine and uracil Purines= adenine and guanine
What is nearly always true about mutations?
They originate in DNA but their effects are shown through proteins - it is chemical modifications that cause changes to DNA
How many mutations occur per day ?
In every cell about 100 mutations occur in the body per day - most of them dont matter
What are the different types of mutations?
deletions, insertions and point mutations
Synonymous= made a change to codon but no change to amino acid
Non-synonymous= change in the codon which causes a change in the amino acid
- non-sense= truncating the protein early
-missense= substituting an aa for another one
chromosome rearrangment- often occurs in leukemias
copy number variants- Her2- entire gene is duplicated more
epigenetic mutation- ER alpha- not all mutations occur in DNA
What are the different mechanisms of mutations?
Spontaneous chromosome re-arrangment
Gene amplification
Random errors in replication= mistakes when DNA is replicated
Inheritance- common mutations e.g. brac-2 in breast cancer is highly inherited
Viruses- this was how oncogenes were first discovered
Environmental exposure- chemical mutagens and radiation
What are some causes of mutations ?
OXIDATIVE DAMAGE of DNA by ROS
- hydrogen perioxide, hydroxyl radicals and superoxide radicals
These ROS can arise from irradiation or they can be produced by aerobic metabolism
Environmental chemicals
- chemicals present in tobacco
- product of industrial activity
- resulting from metabolism of food components
- cooking food- way food is prepared
What are the 2 types of genomic DNA cells contain?
either contain 1 set of genomic DNA= germ cells
or they contain 2 sets of genomic DNA= regular diploid cells
what can defects and ineffiences in DNA repair systems lead to ?
it can increase the number of mutations
How effective are DNA repair systems ?
due to DNA repair systems, less than 1 incident of DNA damage in 1000 hits becomes a mutation
if mutations occur in the repair systems then this is very bad- causes cells to be prone to developing lots of mutations
What is the base-excision repair system ?
this cuts out the entire base
types of damage: basic sites, free radical oxidation or deamination of cytosine/methylcytosine
What is base mis-match repair?
notices irregular DNA so it replaces the base
types of damage: small adducts, free ROS, insertions/deletions
What is the nucleotide excision repair?
replace sugar aswell
types of damage: large adducts and UV cross links
What is alkyl transferase?
it is an enzymes
types of damage: small alkyl adducts
What is homologous recombination?
this only occurs in homologous recombination
types of damage: strand breaks
What happens if mutations are not repaired?
then there is an increased risk of cancer - it is proportional to mutation rate
What are the 3 classes of genes frequently mutated in cancer ?
PROTO-ONCOGENES= they can become mutated forming oncogenes. Normally they are important in making cells divide and grow
TUMOUR SUPPRESSOR GENES- these stop genes dividing
GENES LINKED TO MUTATION RATE
Define oncogene:
gene that has the potential to cause cancer
Define tumour suppressor gene:
gene that protects cells from one step on the path to cancer
Define mutator genes:
gene that increases the rate of mutation of one or more other genes
How long does the cell cycle take ?
18-24 hours- it is tightly regulated
Why are most cells not going through the cell cycle?
They are terminally differentiated
They are senescent
They are quiescent in G0 phase
What happens in the G1 phase ?
the cell becomes responsive to growth factors - period in which cell is responsive to mitogenic growth factors and TGF-beta
TGF-beta is often mutated in cancer
Where is the R point and what happens?
R point is within the G1 phase and its the point when cell stops becoming responsive to signals
What are 2 key points about cancer cells and growth signals?
cancer cells are self-sufficient in growth signals and insensitive to anti-growth signals
