cancer chemotherapy

Question 1

The nitrogen mustards (Alkylating agents) contain highly electrophilic groups and form covalent bonds to nucleophilic groups in DNA. true or false?

Answer 1

true

Question 2

alkylating agents are useful anti‐tumour agents that prevent replication and transcription. true or false?

Answer 2

true

Question 3

alkylation of nucleic acid bases can result in miscoding. TRUE OR FALSE?

Answer 3

TRUE

Question 4

what are the toxic side effects of alkylating agents?

Answer 4

alkylation of proteins

Question 5

what does Melphalan mimic?

Answer 5

phenylalanine and is transported into cells by normal transport proteins

Question 6

The uracil ring in uracil mustardis electron withdrawingand so this is a less reactive alkylating agent. true or false?

Answer 6

true

Question 7

what does the uracil ring mimic?

Answer 7

• nucleic acid base

- is concentrated in fast growing cells

Question 8

what group in estramustine is electron withdrawing?

Answer 8

urethane group

Question 9

what is the most commonly used alkylating agent?

Answer 9

Cyclophosphamide

Question 10

Cyclophosphamide is a non‐toxic prodrug which is orally active. true or false?

Answer 10

true

Question 11

what is the by-producted of the activated Cyclophosphamide by alkylation and what is it associated with?

Answer 11

Acrolein

- Associated with toxicity

Question 12

what is the most clinically toxic anti-cancer drugs?

Answer 12

• Mitomycin C

Question 13

Mitomycinis also a prodrug activated in vivo to form an alkylating agent. true or false?

Answer 13

true

Question 14

is cisplatin a prodrug?

Answer 14

• yes

Question 15

when is cisplatin activated?

Answer 15

is activated in cells with low chloride ion concentration

Question 16

cisplatin binds to DNA in regions rich in guanine units. true or false?

Answer 16

true

Question 17

what kind of strands does cisplatin form that causes localised unwinding of the DNA double helix and inhibits transcription?

Answer 17

Intrastrands

Question 18

anthracyclines are what types of agents?

Answer 18

Intercalating agents

Question 19

The planar anthraquinone of anthracyclines moiety intercalates between the DNA base pairs and the carbohydrate moiety binds into the minor groove. true or false?

Answer 19

true

Question 20

5‐Fluorouracil(5‐FU) is a prodrugthat is metabolised to give 5‐F‐dUMP which then acts an inhibitor of thymidylatesynthase. True or false?

Answer 20

true

Question 21

How does 5‐F‐uDMP inhibits thymidylate synthase?

Answer 21

• The C-F bond is stronger than the C-H bond which is normally cleaved by thymidylatesynthase
• This causes the enzyme to be inhibited irreversibly

Question 22

Capecitabineis a produgof 5‐fluorouracilwhich is itself a prodrug. true or false?

Answer 22

true

Question 23

what is the only chemotherapy drug availabe for treatment of pancreatic cancer?

Answer 23

• Gemcitabine

Question 24

Gemcitabine is the fluorinated analogue of 2’‐deoxycytidine and it interacts with DNA and RNA polymerases within the cancerous cell which inhibits nucleic acid replication and repair. TRUE OR FALSE?

Answer 24

TRUE

Question 25

what are kinases?

Answer 25

- They are enzymes that catalyse phosphorylation

Question 26

overexpression of kinases can lead to cancers. true or false?

Answer 26

true

Question 27

give examples of type 1 and type 2 kinase inhibitors?

Answer 27

- Type 1 - gefitinib | - type 2 - Imatinib

Question 28

how do type 1 and 2 kinase inhibiotrs work?

Answer 28

- Type 1: - bind to the active conformation of the enzyme - inhibitors bind to the ATP binding site and block access to ATP - Type 2: - act on the inactive conformation of the enzyme - bind to the enzyme and stabilise the inactive conformation

Question 29

which are more likely to be selective between type 1 and 2 kinase inhibitors?

Answer 29

- Type 2

Question 30

there is a greater risk that random mutation of the target will weaken binding interactions and lead to drug resistance with type 2 kinase inhibiotrs are they are ore selective. true or false?

Answer 30

true

Question 31

type III inhibitors bind to regions of the active site not occupied by ATP. true or false?

Answer 31

true

Question 32

the EGF‐receptor of gifitnib is a tyrosine kinase receptor. true or false?

Answer 32

true

Question 33

how does gefitinib work?

Answer 33

It inhibits the kinase active site of the epidermal growth factor receptor

Question 34

gefitinib the morpholine ring increases water solubility. true or false?

Answer 34

true

Question 35

Imatinib is a selective inhibitor for a hybrid tyrosine kinase (Bcr‐Abl)which is active in certain tumour cells. true or false?

Answer 35

true

Question 36

what increases the activity, selectivity and water solubility in Imatinib?

Answer 36

piperazine

Question 37

list the different types of cancer chemotherapy classes of drugs?

Answer 37

- Alkylating agents - Kinase inibitors - platinum compounds - Mitomycin C - Thiopurines - inhibitors of thymidylate synthase - Intercalating agents - Dna polymerases