Cancer

Question 1

types of cancer

Answer 1

1. carcinoma
2. sarcoma
3. leukaemia
4. neuroectodermal

Question 2

carcinoma

Answer 2

malignant tumours of epithelial cells

• include:
  (i) adenocarcinoma (arising in glandular epithelial tissue)
  (ii) basal cell carcinoma
  (iii) squamous cell carcinoma
  (iv) transitional cell carcinoma

Question 3

sarcomas

Answer 3

• tumours of tissues derived from mesenchymal cells ((mainly connective tissue) muscle, fat, bone, cartilage, blood vessels etc.)
• highly malignant

Question 4

leukaemias

Answer 4

• abnormal proliferation of WBCs
• its haematopoetic
• subtypes:
  (i) lymphoma (lymphocytes)
  (ii) myeloma

Question 5

the hallmarks of cancer— cell intrinsic

Answer 5

1. growth signalling autonomy
2. resistance to growth inhibitory signals
3. Unlimited replicative capacity
4. reprogramming of cell metabolism
5. resistance to apoptosis
6. genetic instability

Question 6

the hallmarks of cancer—cell extrinsic

Answer 6

1. induction of angiogenesis
2. metastatic potential
3. evasion from immune surveillance

Question 7

neoplasm

Answer 7

is an abnormal cell growth-a tumour

may be benign or malignant

Question 8

benign tumour examples

Answer 8

• adenoma
• carcinoma in situ (commonly cervical and skin)
• fibroma
• hyperplasia
• dysplasia
• metaplasia

Question 9

angiogenesis

Answer 9

it’s a normal process required by the body for wound healing; the angiogenesis programme is hijacked by tumour cells

ex.
- tumour cells secrete VEGF (vascular endothelial growth factor)
- VEGF binds to the endothelial cells lining blood vessels and causes them to secrete MMPs which allows their remodelling
- the activated endothelial cells proliferate and migrate towards the source of VEGF, i.e. tumour
- the endothelial cells also secrete PDGF (platelet derived growth factor) which is a chemoattractant for smooth muscle cells

Question 10

what is the angiogenic “switch” in tumours

Answer 10

• normal angiogenesis is balanced by pro- and anti-angiogenic factors;
• as tumours release angiogenic factors, this balance is thrown off

Question 11

what are the activators and inhibitors in the angiogenic

“switch”?

Answer 11

Activators:
FGF, IGF, HGF, VEGF, PDGF-BB

inhibitors:
Angiostatin, Endostatin

Question 12

example of a solid tumour that is not angiogenic

Answer 12

PDAC– pancreatic ductal adenocarcinoma
it’s largely avascular and hypoxic

note: in PDAC, due to lack of vascularity the delivery of therapeutic drugs is compromised

Question 13

epigenetic causes of cancer

Answer 13

1. changes in chromatin
2. post-translational modifications of proteins (changed stability or activity of proteins that are involved in genesis/maintenance of transformed cells)
3. control of transcription or translation
   (i) long non-coding RNAs=> modify transcription or translation of mRNAs
   (ii) microRNAs=>(miRNAs) are 18-24 nucleotides in length and inhibit translation of specific proteins, some of which may be involved in cancer

Question 14

are miRNAs oncogenes or tumour suppressor genes?

Answer 14

• particular miRNAs are either increased or decreased in tumours
• when a certain miRNA expression is increased in tumour cells they’re thought to act as “oncogenes” by inhibiting the expression of endogenous tumour suppressor genes
• whereas, when a certain miRNA expression is increased in normal cells and decreased in tumour cells then thought to act as “tumour suppressors” by inhibiting oncogene expression

Question 15

angiogenesis inhibitors

Answer 15

Avastin (bevacizumab)– a monoclonal antibody against VEGFA

-Limited success; poor efficacy and side effect– withdrawn from treatment of metastatic breast cancer

Question 16

notes on tumour expansion

Answer 16

• angiogenesis
• neo-vasculature is leaky and tortuous–unstable blood flow
• hypoxia in centre–necrotic core; outer regions continue growth
• can recruit normal host cells esp those associated with inflammatory and immune responses– Macrophages and lymphocytes
• these can be stimulated to produce growth factors and other proteins–therefore, enhance the proliferation and survival of tumour cell

Question 17

notes on invasion and metastasis

Answer 17

primary tumours– well defined boundaries; surgically retractable; local recurrence may occur if incomplete removal!

(the fatality comes from metastasis!!!)

Metastatic tumours

• cells in tumours make proteases- degrade basement membrane and invade host cell
• also enter blood/lymph
• extravasate (exit these vessels) to form secondary metastatic lesions

NOTE: the metastatic tumours DO NOT usually show genetic changes in comparison to the primary tumour