PoD - Cancer

Question 1

define cancer

Answer 1

• carcinoma or disorderly growth of cells which invade tissue and adjacent tissues
• can spread via lymphatics and blood vessels to other parts of the body

Question 2

how do cancer cells divide?

Answer 2

• cells undergo normal mitosis, however, at some stage the cell gains a mutation that means it cannot be regulated
• altered cell continues to grow and divide creating a large population of mutated cells (tumour)

Question 3

what is the difference between normal and cancer cells?

Answer 3

• normal cells are uniformed/ordered, cancer cells are abnormal/disordered
• normal cells maintain cell-cell junctions, cancer cells lose contact inhibition (invade)
• normal cells oncogene expression is rare, cancer cells have an increase in oncogene expression
• normal cells have intermittent GF secretion, cancer cells have increase in GF secretion
• normal cells possess tumour suppressor genes, cancer cells have lost tumour suppressor genes
• cancer cells have increased blood vessel formation

Question 4

is cancer multi-staged?

Answer 4

• yes
• carcinogen causes mutation
• initiation stage where mutated cells present (body will get rid of or continue to form tumour)
• promotion stage (mass of abnormal cells)
• tumour growth (blood vessel formation)
• progression to clinical cancer (isolated or metastases)

Question 5

what are the main causes of cancer?

Answer 5

• chemical
• physical
• viral
• promoting factors (GFs , oncogenes)
• progressive factors (metastases)

Question 6

what are tumour suppressor genes?

Answer 6

• normal function is a transcriptional regulator, promotes DNA repair, apoptosis
• tries to get rid of mutated cells before they cause problems (present at G1/S checkpoint)
• normally induced by DNA damage and hypoxia

Question 7

how does non-squamous NSCLC (non-small cell lung cancer) develop? targets/therapy

Answer 7

• ALK (tyrosine kinase receptor) - translocation occurs which means a tyrosine inhibitor can be used to stop and shrink the cancer
• EFGR - changes within the gene can make individuals more/less sensitive to treatment

Question 8

how can cancers invade and metastasise?

Answer 8

• tumour invades through basement membrane
• move into extracellular matrix/connective tissue/surrounding cells
• invades blood vessels
• tumour cells spread in distant organ
• many enzymes are involved in the process (ECM - matrix metalloproteinases; plasmin; cathepsin/ cell adhesion - cadherins (loss = tumour invasion)/integrins)

Question 9

how is angiogenesis related to cancer?

Answer 9

• new blood vessels must form in order for a tumour mass to grow
• clinical correlations are seen between angiogenesis & vessel density/tumour malignancy/metastasis

Question 10

how can molecular biology be used in therapeutics?

Answer 10

• example of VEGF
• Avastin is an anti-VEGF antibody that has been produced for clinical use
• avastin prevents GF interaction with receptors and therefore prevents activation of downstream signalling pathways
• anti-VEGF therapy normalises vasculature
• involved in vascular regression and tumour dormancy

Question 11

how does our immune systems not recognise cancer?

Answer 11

• cancer cells can hide from T cells
• PD1 (programmed death receptor) is present on T lymphocytes
• PDL-1 is on tumour cells
• Interaction of these suppresses T cell action (inhibits immune response)
• nivolumab is a PD-1 inhibitor that prevents the T cell PD-1 receptor binding to the tumour ligand