Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cancer > Cancer Chemistry > Flashcards

Cancer Chemistry Flashcards

1
Q

What is the most important target out of the 4 bases for anti cancer therapies?

A

N7 atom of guanine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What happens when the N7 atom of guanine is alkylated?

A

It becomes positively charged and the charge is stabilised by resonance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are DNA lesions?

A

They are chemically altered bases which can be caused by Reactive oxygen species, radiations or chemicals and also spontaneous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the difference between a monofunctional and a bifunctional akylating agent?

A

point mutations versus major deletions DNA strand breakage and hyper recombination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the difference between an intrastrand, and an interstrand, cross-link?

A

Intrastrand is within a strand and interstrand is between opposite strands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Why are interstrand cross links particularly cytotoxic?

A

Prevent replication and transcription by preventing the parting of two DNA strands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the difference between mutagenic and clastogenic agents?

A

Clastogenic are those that can cause damage on a chromasomal level rather than DNA level.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Nitrogen mustards don’t always form bisadducts. What side reaction can occur, resulting in the formation of monoadducts?

A

n N7-alkylated guanine derivative (11) as shown in Figure 6. This guanine monoadduct can then form another reactive aziridinium intermediate, which can react either with water to form a 2-hydroxyethyl monoadduct

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Interstrand cross-links formed by nitrogen mustards distort the DNA structure, e.g. they may bend it. Can you explain why?

A

The minimal distance between the guanines in this sequence is approximately 6.8 Å in B-form DNA, which is more than the 5.1 Å distance that can be spanned by the five atoms that comprise the cross-link

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Why technically speaking is the phosphoramide group not an alkylating agent?

A

Because the phosphoramide electron withdrawing group means the nitrogen lone pair is not available for formation of the azridinium ion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Why is phosphoramide mustard an active alklating agent, when cyclophosphamide is not?

A

Because the phosphoramide group is less electron-withdrawing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How do anthacyclines work?

A

Instead they interact non-covalently with the DNA.

The planar anthracycline rings insert between the planes of successive base pairs – a process called intercalation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

“Many cytotoxic antibiotics act as radiomimetics and simultanous use of radiotherapy should be avoided because it may markedly increase toxicity”

Why?

A

Both produce similar modes of action and can effect healthy cells if over concentrated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which pathways are primarily used for the repair of double strand breaks?

A

Homologous recombination

Non-homologous end joining

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does ionising radiation cause DNA damage? Which of the following statements are true in relation to IR induced DNA damage?

A

Reactive oxygen species (ROS) are produced which react with DNA
Bases are modified (e.g. 8-OxoG)
Double strand DNA breaks occur
Single strand DNA breaks occur

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Temozolomide (TMZ) doesn’t directly cause double strand DNA breaks, however lethal DSBs result from the futile attempts of the cell to repair TMZ induced DNA damage. What type of DNA lesion does TMZ cause that ultimately results in DSBs?

A

Methylation

17
Q

Which DDR (DNA damage repair) pathway is required for these DSBs (double stranded breaks) to result?

A

MMR DNA mismatch repair

18
Q

Which protein has been identified as being involved in TMZ resistance, and also as a target for potentiation of TMZ (albeit with unacceptable side effects)?

A

MGMT O6-methylguanine DNA methyltransferase

19
Q

The paper discusses the targeting of proteins involved in double strand repair as a strategy for increasing the sensitivity of cancers to radiotherapy.
a. Which protein required for HR is suggested as a target for radiosensitization?

A

ATM

20
Q

The paper discusses the targeting of proteins involved in double strand repair as a strategy for increasing the sensitivity of cancers to radiotherapy.
b. Which protein required for NHEJ is suggested as a target for radiosensitization?

A

DNA-PK

21
Q

The paper discusses the targeting of proteins involved in double strand repair as a strategy for increasing the sensitivity of cancers to radiotherapy.
c. Which checkpoint signalling protein is suggested as a target for radiosensitization?

A

Chk-1

22
Q

Topoisomerase inhibitors cause DNA breaks by preventing the religation of DNA during conformational reorganisation.
Which out of camptothecin or etoposide would you expect to be more toxic to a slowly proliferating cancer?

A

Etoposide

23
Q

Which DDR pathway is involved in the repair of intrastrand crosslinks?

A

NER

24
Q

What condition can be exploited to kill cancer cells in which one DDR pathway is lacking (for example due to mutation)?

A

Synthetic lethality

25
Q

What are the purines?

A

Adenine and guanine

26
Q

What is the difference between purines and pyridines?

A

Purines are bicyclic heterocycles whereas purines are monocyclic

27
Q

Name two of the most common alkylating agents

A

Bendamustine and cyclophosphamide

28
Q

What is intercalation?

A

Planar anthracycline rings insert between the planes of successive base pairs - this is when the molecules (daunomycin and doxorubicin) don’t form covalent bonds to DNA but instead interact non-covalently - this is how anthacyclines work

29
Q

What is the difference between TOP I and II?

A

1 works of single strand DNA whereas II works on double strand

30
Q

What makes anthacyclines cytotoxic?

A

Intercalation process itself isn’t cytotoxic - it comes from the anti tumour activity activated by this which encourages Topoisomerase which releases DNA tension and causes it to become single stranded

31
Q

Which pathways are primarily used for the repair of double strand breaks?

A

Homologous recombination and non-homologous end joining

32
Q

What is camptothecin?

A

Targets the complex between DNA and TOP 1

Topotecan is a semi-synthetic analogue that’s clinically used - more soluble as has a basic group

33
Q

How does cisplatin and oxaliplatin work?

A

Bind covalently to DNA via their platinum atom - this forms cross links and disrupts both strands

34
Q

What are the two anti hormonal strategies?

A

Inhibit estrogen biosynthesis or create an estrogen receptor antagonist

35
Q

How does tamoxifen act as an ER antagonists over diethylstilbesterol?

A

Bind much more strongly to oestrogen receptors - act as an antagonist rather than agonist due to extra bulk in its structure compacted to DEF.
Extra bulk means co-activator cannot bind

36
Q

What drugs inhibit estrogen biosynthesis?

A

Aromatise inhibitors: letrozole, anastrozole and exemestane

Cancer (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions