Lecture 20 - Introduction fo Radiotherapy and Radiobiology NOT FINISHED

Question 1

What are the 5R’s of radiobiology?

Answer 1

1. repair
2. repopulation
3. redistribution
4. reoxygenation
5. radiosensitivity

Question 2

Describe repair

Answer 2

• radiation cures cancer by causing DNA damage
• radiation –> ionisation of water molecules, charged –> DS breaks (difficult to repair)
• differential DNA damage repair between cancer tissue and normal tissue

Question 3

Describe repopulation

Answer 3

• we give radiotherapy over long time
• during treatment see changes in cellular dynamics
• kill some cells off, regrowth of existing tissue –> failure
• stimulated by release of inflammatory cutlines and arachidonic acid and prostaglandin E2

Question 4

Describe redistribution

Answer 4

• cells progress through cell cycle from G1 –> S –> G2 –> mitosis
• during radiation therapy, cells distribute themselves into different stages of the cell cycle in response to DNA damage
• different stages are more sensitive to radiation induced killing than others
• the most radiosensitive is G2, two copies of genome and about to go through mitosis. These cells entire mitosis with catastrophic levels of DNA damage –> death
• in G1, has whole of S phase to repair damage before mitosis

Question 5

Describe reoxygenation

Answer 5

• centre of tumours are hypoxic, tumours have poor blood supply
• hypoxia switches on genetic programme that leads resistance to cell death, invasion into other tissues, resistance to DNA damage, reduced radiosensitivity
• cells on outside die first, less competition to centre, centre then more sensitive to radiotherapy

Question 6

Describe radiosensitivity

Answer 6

• catch all for everything else we don’t understand
• different types of cancer have different intrinsic sensitivities
• poorly understood

Question 7

What hallmarks of cancer can repopulation and redistribution be mapped onto?

Answer 7

sustained proliferative signalling

e. g. EGFR
- RAS pathway, PI3K pathway

Question 8

What hallmarks of cancer can radiosensitivity be mapped onto?

Answer 8

programmed cell death

e.g. lymphoma

Question 9

How is EGFR involved in DNA repair in the normal and cancer cell?

Answer 9

DNA PK
interacts with broken DNA double helix
EGFR leaves plasma membrane, into nucleus, helps coordinate repair
mutant EGFR, does not internalise