Introduction to Cancer

Question 1

What is cancer

Answer 1

A collection of diseases with the shared underlaying features of uncontrolled cell growth and invasion

Question 2

What is a carcinoma cancer tissue type and give examples

Answer 2

Epithelial

Breast lung and liver

Question 3

What is a sarcoma cancer tissue type and give examples

Answer 3

Connective tissue

Bones (osteocytes) , muscle, blood vessels

Question 4

What is a myeloma and leukaemia cancer tissue type and give examples

Answer 4

Bone marrow for both of them

Myeloma: Plasma cells (white blood cells that secrete large volumes of antibody)

Leukaemia: White blood cells, erythrocytes

Question 5

What is a lymphoma tissue type and give examples

Answer 5

Lymph nodes and glands

Spleen, tonsils, thymus

Question 6

Which cancer has the highest and lowest survival rate

Answer 6

Non melanoma (highest survival rate)

Melanoma: High to moderate survival rate

Breast and bladder: Moderate survival rate

Lung and pancreas: lowest survival rate

Question 7

Define Neoplasm

Answer 7

Disorganised growth with net increase in number of dividing cells (similar to tumour swelling)

Question 8

Define Malignant tumour

Answer 8

Not benign and spread beyond initial site

Question 9

Define benign tumour

Answer 9

Do not invade surrounding tissue, nor spread

Causes problem when pressing against cell walls

Question 10

Define Metastasis

Answer 10

Invasion of a tumour to its surrounding tissue and spreads beyond original site

Question 11

Briefly describe each stage of the cell cycle

Answer 11

1. M Phase: Prophase, metaphase, anaphase, telophase
2. G1: RNA and protein synthesis
3. S: DNA synthesis
4. G2: cell growth continues

Question 12

Explain all steps of M phase

Answer 12

Prophase: chromosome condense, centrosomes assemble

Metaphase: Chromosomes align and attach to spindle

Anaphase: Chromotids pull apart and migrate to poles

Telophase: Chromotids decondense, new nuclear membrane made

Cytokinesis: nuclear membrane decondenses, dividing cytoplasm of mother cell, two daughter cells made

Question 13

What are the positive regulators of the cell cycle

Answer 13

G1: CDK4/6 (cyclin)

R point (restriction point): can only go through if you have CDK4/6

S phase: E-CDK2, A-CDK2, A-CDC2

G2 Phase: B-CD2

Then you can go to M phase

Question 14

What are the factors that control cyclin complexes

Answer 14

E2F transcription factors

pRB proteins

Question 15

One of the hallmarks of cancer is gaining growth factor independence, describe this?

Answer 15

1. Cells lose requirement for growth factors to stimulate cell division (gain an oncogene which stimulates cancer)
2. Includes:
   Growth factor that is normally secreted by surrounding tissue
   Mutation in growth factor so it is continually activated
   Mutation of components of signalling pathways or transcription factors activated
3. Gains an oncogene- important in regulation of cell proliferation and lead to growth factors signal always on

Question 16

What is an oncogene and give an example of the most popular one

Answer 16

1. Term given to a mutated or over expressed gene that causes cancer
2. Example: Ras- normally in growth signals it leads to signalling events that trigger cell proliferation
3. In cancer Ras is constantly on

Question 17

Give examples of other oncogenes that are not as common

Answer 17

1. Bcr-Abl
2. myc
3. src
4. P13 kinase

Question 18

Give an example of a drug that targets growth factors

Answer 18

Imatinib

A Tyrosine kinase inhibitor that prevents growth factor signals which promote cell proliferation

Question 19

Give an example of growth factor independence in breast cancer and how to counter it

Answer 19

HER2 (human epidermal growth factor receptor 2): amplified in breast cancer

Counter: Trastuzumab (Herceptin) blocks it

Question 20

One of the hallmarks of cancer is gaining insensitivity to growth inhibitors, describe this

Answer 20

1. Cells lose ability to control abnormal cell proliferation
2. This occurs due to alteration in cell cycle regulation which causes loss of TUMOUR SUPPRESSOR GENE
   and UPREGULATION of positive cell cycle regulators such as CDC25 or cyclins

Question 21

How do tumour suppressor genes perform is function and give examples of them

Answer 21

Complete opposite to oncogenes and prevent tumours from forming through detecting DNA damage and mutations, then triggering apoptosis or DNA repair

Examples: pRB, p53 (most commonly mutated in cancer), BRCA

Question 22

What is the role of p53?

Answer 22

1. Acts against lack of nucleotides, UV radiation, ionising radiation, oncogene signalling, hypoxia, blockage of transcription
2. Reacts by: cell cycle arrest (stops cell dividing or continue), DNA repair, block of angiogenesis, apoptosis

Question 23

One of the hallmarks of cancer is proliferation without limit, describe this

Answer 23

1. Most cells cannot proliferate indefinitely due to limitation in telomere length (shortens after every proliferation, stick and go through cell death)
2. Tumour cells are immortal through production of Telomerase which rebuilds back telomeres

Question 24

One of the hallmarks of cancer is avoiding apoptosis, describe this?

Answer 24

1. Triggered by DNA damage and viral infections
2. Gain resistance through pro survival factors such as Bc12
3. Loss of function of pro-apoptotic factors like p53

Question 25

One of the hallmarks of cancer is promoting angiogenesis, describe this

Answer 25

1. Tumours stay small until they secure a blood supply 2. Provides increased blood supply (nutrients) to tumour to allow continued growth 3. Promotes new blood vessel formation through secretion of angiogenic factors

Question 26

Give examples of angiogenic factors

Answer 26

1. Vascular Endothelial Growth Factor (VEGF) | 2. Fibroblast Growth Factor (FGF)

Question 27

One of the hallmarks of cancer is invasion and metastasis, describe this?

Answer 27

1. 90% of cancer deaths occur due to cancer spreading to distant sites 2. Additional cellular changes is necessary for cancer to overcome containment mechanisms 3. Ability to break away from main tumour form metastatic tumours in different areas of body Pancreas -> Lungs Breast -> Lungs, liver or bone 4. Able to do this through decreased cell adhesion molecule expression or protease secretion to break ECM 5. Move via lymphatic vessels or blood

Question 28

What are the different types of gene mutations

Answer 28

1. Gene coding regions 2. Alterations in transcription or splicing 3. Amplifications and deletions of chromosomal regions 4. Chromosomal translocations 5. Gain and losses of whole chromosomes 6. Changes in DNA modification

Question 29

What causes DNA mutations

Answer 29

``` UV Free radicals Viruses- hepatitis B/C, T cell leukaemia virus Chemicals Copying and repair errors ```

Question 30

What are the three stages of cancer development and describe them

Answer 30

1. Initiation: mutation firstly promotes increased proliferation (Carcinogenesis) 2. Promotion: additional mutations promote further proliferation (carcinogenesis) 3. Tumour progression: Growth and invasion of tumour

Question 31

Describe the ranks of cancer stages from 1-4?

Answer 31

1. Small size not spread 2. Moderate size, spread to nodes 3. Large size, spread to nodes 4. Large size, wide spread

Question 32

What are the risk factors for cancer

Answer 32

``` Smoking Inactivity Lack of activity Alcohol lack of fruit and veg red meat Salt INFECTIONS: 18% of all cancers ```