Outline of Cancer Disease Process

Question 1

Define cancer

Answer 1

Carcinoma or disorderly growth of epithelial cells which invade adjacent tissue and spread by the lymphatics and blood vessels to other parts of the body

Question 2

What type of cells does cancer usually arise from?

Answer 2

Epithelial, only 20% arise from non-epithelial connective tissue, musculoskeletal or nervous tissues

Question 3

How can you differentiate between normal and cancerous cells using a microscope?

Answer 3

• Lots of blood vessels (increased angiogenesis)
• Cells at different stages of the cell cycle
• Abnormal heterogeneous cells
• Irregular and messy borders
• Irregular nuclei

Question 4

Describe the three stages of carcinogenesis

Answer 4

o Initiation – irreversible genetic damage to cells that proliferate and survive for the lifetime of the organism
o Promotion – reversible changes that increase chances of it progressing to cancer, including the selective clonal expansion of the initiated cells. This is aided by growth factors and oncogenes
o Progression – irreversible malignant conversion of the initiated prenoeplastic cell into one that expresses the malignant phenotype

Question 5

How large does a tumour have to be before it is usually detected?

Answer 5

1cm

Question 6

What can initiate carcinogenesis?

Answer 6

o Chemical carcinogens
o Physical carcinogens
o Viral carcinogens

Question 7

Describe some chemical carcinogens that can initiate cancer development

Answer 7

Chemical carcinogens:
• Polycyclic hydrocarbons and soot on scrotal cancer
• Anilene dyes and bladder cancer
• Aflatoxin (mouldy peanuts) and liver cancer
• Nitrogen mustard and leukaemia
• Alcohol and smoking

Question 8

Describe some physical carcinogens

Answer 8

Physical carcinogens:
• Ionising radiation – dose response relationship, affects chromosome translocation, influences gene amplification and activated oncogenes

Question 9

Describe some viral carcinogens

Answer 9

Viral carcinogens:
• Herpes virus and Burkitts lymphoma
• Human papillomavirus and cervical cancer
• Retroviruses HTLV1 and HTLV2 on leukaemia + lymphoma
• Hepatitis B and liver cancer

Question 10

What causes cancer promotion?

Answer 10

Mutations in either

• protoonocogenes e.g. Bcl2 activation
• growth factors
• tumour suppressor genes e.g. p53

Question 11

What is Bcl2?

Answer 11

Bcl2 is a protooncogene, activation prevents apoptosis

Question 12

What is p53?

Answer 12

Tumour suppressor gene, is the most commonly altered gene in human tumours (37% but higher in lung and colon).

Question 13

What is the normal function of tumour suppressor genes?

Answer 13

Normal function is as transcriptional regulator; promotes DNA repair, apoptosis, differentiation

Question 14

What usually causes genetic mutations?

Answer 14

DNA damage and hypoxia

Question 15

What enzymes allow the spread of cancer into the ECM?

Answer 15

• Matrix metalloproteinases (MMPs)
• Plasmin
• Cathepsin

Question 16

What cell adhesion molecules are affected during invasion by tumour cells?

Answer 16

• Cadherins
• Integrins
• CD44

Question 17

What type of imaging is particularly useful when testing for metastases?

Answer 17

PET

Question 18

How big can a tumour get without the requirement of angiogenesis?

Answer 18

2mm

Question 19

What is Avastin (bevacizumab)?

Answer 19

• The humanised anti-VEGF MAb Avastin (bevacizumab) prevents the interaction of VEGF with its receptors, VEGF receptor-1 and VEGF receptor-2 on the surface of vascular endothelial cells.
• This prevents activation of the VEGF receptors and of the downstream signalling pathways that would normally lead to the growth, proliferation, migration and survival of endothelial cells of the blood vessels.

Question 20

What is PDL1?

Answer 20

• Programmed death-ligand 1 (PD-L1) is a 40kDa type 1 transmembrane protein that has been speculated to play a major role in suppressing the immune system during particular events such as pregnancy, tissue allografts, autoimmune disease and other disease states such as hepatitis.
• PDL-1 has now been found to be expressed on some tumour cells

Question 21

What drug targets PDL1?

Answer 21

atezolizumab

Question 22

What is atezolizumab?

Answer 22

PDL1 MAb

Question 23

What is ipilimumab?

Answer 23

Ipilimumab is a monoclonal antibody that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

Question 24

What drug targets CTLA4?

Answer 24

Ipilimumab

Question 25

What immune checkpoints are targeted in cancer treatment?

Answer 25

CTLA4 - suppresses immune response

PDL1 - suppresses immune response