MT L3 New targets

Question 1

5 New targets

Answer 1

1. potentiate DNA damaging therapies
2 .target hypoxia
3. target angiogenesis
4. target signalling - especially cell cycle control
5. inhibit elongation of telomeres

Question 2

-what sort of lesions?

Radiotherapy and bleomycin

Answer 2

single/double strand breaks
damage to bases

(repaired by NHEJ, SSBR, BER, HR)

Question 3

Repair bathways

Answer 3

NHEJ - repaired by non-homogolous end joing
BER - base excision repair
SSBR - single strand break repair
HR - homogolous recombination

Question 4

6 DNA damaging therapies that could be the focus of potentiation

Answer 4

Radiotherapy/bleomycin
Mono-alkylators
Cross-linkers
Topoisomerases
Reblication inhibitors
Antimetabolites

Question 5

How does o6-benzylguanine work?

Answer 5

direct inhibition of MGMT (repair enzyme)

Question 6

Name three drugs that inbhibit a control system (and their targets)

Answer 6

1. Olaparin inhibits PARP-1
2. XL844 inhibits checkpoint kinase (CHK)
3. NU7441 inhibit DNA0dependant protein kinase (DNAPK)

Question 7

Basis of selectivity of most cancer therapies is just

Answer 7

increased growth

Question 8

tumour vasculature is characterized by….

Answer 8

diorganised network
vessel walls not well formed
leaky
high interstitial pressure

Question 9

nae the three regions if the rumour

Answer 9

Oxic
hypoxic
necrotic

Question 10

Decribe oxic region

Answer 10

well oxygenated, proliferating. this is the part of the tumour sensitive to therapy (radio and chemo)

Question 11

Describe the hypoxic region

Answer 11

low oxygen concentration
not proliferating
insenstive to therapy
(they are in G0 phase)

Question 12

decrbe the necrotic region

Answer 12

cells are dead, they wont come back so it’s not a problem

Question 13

in what sized tumours is there three regions?

Answer 13

> 1mm

Question 14

radioation therapy requires what sort of tissues

Answer 14

oxygenated

Question 15

3 ways the hypoxic region coulg be a theraputic oportunity

Answer 15

Radiosensitising drugs (PARP-1 inhibitors & pimonidazole)
Hypoxia-selective drugs (nitroimidazoles and mitomycon)
EPR effect (soluble polymeric prodrugs accumulate where there is no lymph drain)

Question 16

How do we inhibit angiogenesis

Answer 16

inhibitors of kinase activity (sunitinib)
neutralising antibodies (avastin)
Parp-1 inhibitors (via inhibition of NFKB)

Question 17

how does avastin work

Answer 17

antibody against VEGF - signal for angiogenesis

Question 18

how can we interfer with signalling/cell cyfcle control

Answer 18

inhibit CDK (seliciclib)
inhibit EGFR tyrosine kinase activity (gefinitib and erlotinib)
inihib Abl kinase (gleevec)

Question 19

inhibit elongation of telomeres

Answer 19

Inhibition of telomerase activity – binding to G-quadruplex

Inhibition of tankyrase-1 – preventing telomerase from binding to telomere