Physiology 2 - Pharmacological Targets for Cancer Therapies (Woolard)

Question 1

What are the general problems with anti-cancer drugs?

Answer 1

Specificity - healthy tissue (especially rapidly proliferating tissue, hair and lining of the gut tissue) is damaged/killed by chemotherapy, as well as the cancerous cells.
Off-target side effects
Tumour cell heterogenity (mix of cells, need multi-targeting)
Drug resistance (Anti-VEGF drug, the body can develop resitance, still all the side effects!)
Dose intensity
Patient-specific factors (diabetes etc, their underlying conditions).

Question 2

What are the main approaches to treatment?

Answer 2

Surgery
Radiotherapy (DNA)
Chemotherapy (DNA, Cell cycle, Topoisomerase, Microtubules)
Targeted therapies (signalling pathways, monoclonal antibodies, receptor tyrosine kinase inhibitors, hormones).

Question 3

What is the goal, at a cellular level, of cancer therapy?

Answer 3

To preserve ‘normal’ metabolism and cell function and to shut down ‘abnormal’ processes that drive growth and proliferation.

Question 4

What are the benefits of surgery?

Answer 4

Best cure for a solid tumour by isolating and removing the whole mass.
Can be used for prevention i.e. removal of moles or pre-cancerous lesions.
‘Debulking’ –> removing maximal mass of the tumour before chemotherapy is started. This may facilitate treatment also i.e. allowing access for the delivery of implanted infusion pumps.

Question 5

What are the disadvantages of surgery?

Answer 5

Invasive, not without risk, patient must be healthy enough for anaesthetic

Question 6

What types of radiotherapy are there?

Answer 6

External beam radiotherapy - from outside the body, using high energy ionising radiation. Commonly used.

Internal brachytherapy - radiotherapy from small radioactive ‘seeds’ placed within the body.

Both cause damage to DNA, normal tissue is also affected.

Question 7

How does chemotherapy combat cancerous cells?

Answer 7

Interfere with the cell cycle - inhibit cellular activities that lead to cell division and replication.
Most commonly, they target wither the S or M phase of the cell cycle.

Question 8

What are phases S and M of the cell cycle?

Answer 8

S : DNA Replication

M : Mitosis - division of two daughter cells

Question 9

What are the different phases of the cell cycle?

Answer 9

G1; production of RNA proteins and enzymes needed for DNA synthesis
S; DNA synthesis
G2; Cell prepared for mitosis (intermediate)
M; mitosis, division to form two daughter cells, DNA condensed into chromosomes
G0; dormant, resting phase
Trigger and the process starts again

Question 10

How do ‘Targeted Therapies’ combat cancer?

Answer 10

Inhibit the interaction of a growth factor/hormone with its receptor e.g. Bevacizumab and VEGF (the antibody binds to VEGF and so the growth factor cannot be agonised.)

Inhibit signalling via receptor e.g. Trastuzumab (Herceptin) and HER-2

Target hormone signalling pathways e.g. Tamoxifen and oestrogen receptor

Question 11

Which rapidly proliferating ‘normal’ cells are affected by anti-cancers in particular?

Answer 11

Gut lining (sickness)
Hair follicles (hair loss)
Immune system cells (immunocompromised)

Question 12

What are the benefits of ‘Targeted Therapies’?

Answer 12

Targeted at specific cancer cells rather than at all rapidly proliferating cells (that includes ‘normal’ functioning ones.