Introduction to Cancer 2

Question 1

What are the 6 hallmarks of cancer ?

Answer 1

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

Question 2

What is cancer and what does it require?

Answer 2

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.

Question 3

In breast tissue what is the most common cell type to develop cancer?

Answer 3

the epithelial cells within the ducts

Question 4

Where else in breast tissue can tumours occur ?

Answer 4

Within the lobules and stroma

Question 5

Why is breast tissue prone to tumourogenesis?

Answer 5

because it is very sensitive to hormonal changes

Question 6

What is the difference between ductal carcinoma and invasive ductal carcinoma?

Answer 6

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.

Question 7

What are the different ways of classifying cancers?

Answer 7

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

Question 8

What are the receptor status’ in breast cancer?

Answer 8

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

Question 9

What is the link between Her2/ErbB2 in breast cancer?

Answer 9

this is a signalling molecule which can change its gene transcription
Perceptin- monoclonal antibody that stops this molecule being activated by its ligand

Question 10

What happens to breast cancer patients that are triple negative?

Answer 10

They dont demonstrate any pathological/histological references, so they are given a horrible concoction of cytotoxic chemotherapeutic drugs

Question 11

What is a mutation ?

Answer 11

it is a changes in DNA- causes changes it how genes behave and their physiology

Question 12

Why are mutations very important ?

Answer 12

They are essential for evolution- they are the raw material of genetic variation

Question 13

What are the types of bases ?

Answer 13

Pyrimidines= cytosine, thymine and uracil
Purines= adenine and guanine

Question 14

What is nearly always true about mutations?

Answer 14

They originate in DNA but their effects are shown through proteins - it is chemical modifications that cause changes to DNA

Question 15

How many mutations occur per day ?

Answer 15

In every cell about 100 mutations occur in the body per day - most of them dont matter

Question 16

What are the different types of mutations?

Answer 16

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

Question 17

What are the different mechanisms of mutations?

Answer 17

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

Question 18

What are some causes of mutations ?

Answer 18

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

Question 19

What are the 2 types of genomic DNA cells contain?

Answer 19

either contain 1 set of genomic DNA= germ cells

or they contain 2 sets of genomic DNA= regular diploid cells

Question 20

what can defects and ineffiences in DNA repair systems lead to ?

Answer 20

it can increase the number of mutations

Question 21

How effective are DNA repair systems ?

Answer 21

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

Question 22

What is the base-excision repair system ?

Answer 22

this cuts out the entire base

types of damage: basic sites, free radical oxidation or deamination of cytosine/methylcytosine

Question 23

What is base mis-match repair?

Answer 23

notices irregular DNA so it replaces the base

types of damage: small adducts, free ROS, insertions/deletions

Question 24

What is the nucleotide excision repair?

Answer 24

replace sugar aswell

types of damage: large adducts and UV cross links

Question 25

What is alkyl transferase?

Answer 25

it is an enzymes

types of damage: small alkyl adducts

Question 26

What is homologous recombination?

Answer 26

this only occurs in homologous recombination

types of damage: strand breaks

Question 27

What happens if mutations are not repaired?

Answer 27

then there is an increased risk of cancer - it is proportional to mutation rate

Question 28

What are the 3 classes of genes frequently mutated in cancer ?

Answer 28

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

Question 29

Define oncogene:

Answer 29

gene that has the potential to cause cancer

Question 30

Define tumour suppressor gene:

Answer 30

gene that protects cells from one step on the path to cancer

Question 31

Define mutator genes:

Answer 31

gene that increases the rate of mutation of one or more other genes

Question 32

How long does the cell cycle take ?

Answer 32

18-24 hours- it is tightly regulated

Question 33

Why are most cells not going through the cell cycle?

Answer 33

They are terminally differentiated
They are senescent
They are quiescent in G0 phase

Question 34

What happens in the G1 phase ?

Answer 34

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

Question 35

Where is the R point and what happens?

Answer 35

R point is within the G1 phase and its the point when cell stops becoming responsive to signals

Question 36

What are 2 key points about cancer cells and growth signals?

Answer 36

cancer cells are self-sufficient in growth signals and insensitive to anti-growth signals