Cancer III

Question 1

What are cell cycle specific drugs?

Answer 1

Antimetabolites

Question 2

What are cell cycle non-specific drugs?

Answer 2

Alkylating agents

Question 3

How do antimetabolites work?

Answer 3

Inhibit DNA/RNA synthesis - S-phase specific

Question 4

What does methotrexate do?

Answer 4

Antimetabolite that is structurally related to folic acid and so inhibits dihydrofolate reductase - targets cells in the S phase

Question 5

What is methotrexate remained as in red blood cells?

Answer 5

MTX-polyglutamate compounds

Question 6

How can the dose of methotrexate be reduced if it is too high?

Answer 6

Leucovorin

Question 7

How are high doses of methotrexate delivered?

Answer 7

IV, IM and intrathecally

Question 8

How does the unchanged drug appear?

Answer 8

In the urine

Question 9

Does methotrexate have poor or good penetration into the CNS?

Answer 9

Poor

Question 10

When is 6-mercaptopurine used?

Answer 10

Maintenance remission in acute lymphoblastic leukaemia and inhibits purine biosynthesis. Incorporated into DNA and RNA leading to non-functional molecules

Question 11

How can resistance to 6-mercaptopurine arise?

Answer 11

Lack of HGPRT or increased drug metabolism

Question 12

What does 6-fluorouracil do?

Answer 12

Deplete intracellular nucleotide pools - interferes with production of dTMP which is needed for DNA synthesis and cell growth

Question 13

What is 6-fluorouracil often given with?

Answer 13

MTX

Question 14

Can 6-fluorourcail cross the BBB?

Answer 14

Yes - excreted in the urine along with metabolites

Question 15

What is gemcitabine an analogue of?

Answer 15

Deoxycytidine - metastatic pancreatic cancer

Question 16

How is gemcitabine administered?

Answer 16

IV and deaminated to a non-toxic product

Question 17

What is a major side effect of gemcitabine?

Answer 17

Myelosuppression

Question 18

What is cytarabine an analogue of?

Answer 18

Cytosine arabinose or AraC that is incorporated into DNA and causes chain termination as no nucleotide can then be added onto it

Question 19

What does dactinomycin do?

Answer 19

Intercalates into the major groove of DNA and interfere with transcription and DNA replication

Question 20

What is dactinomycin used in combination with and why?

Answer 20

MTX as resistance is prevalent due to P-glycoprotein

Question 21

What are the two anthracyclines?

Answer 21

Doxorubicin and daunorubicin

Question 22

What do anthracyclines do?

Answer 22

Intercalate with DNA and generate free radicals that break DNA strands - can also interfere with the dan breakage repair system

Question 23

What are anthracyclines used in combination for?

Answer 23

Lung, breast and leukaemia

Question 24

Where do metabolites of anthracyclines appear?

Answer 24

Bile and urine - poor penetration into the CNS

Question 25

What stage of the cell cycle do anthracyclines target?

Answer 25

S phase and G2 phase

Question 26

What do alkylating agents do?

Answer 26

Transfer alkyl groups to DNA, are mutagens and target rapidly diving cells

Question 27

What do some alkylating agents need for metabolic transformation?

Answer 27

P450

Question 28

What can alkylating agents be used in combination to treat?

Answer 28

Solid and lymphatic tumours | Oral and can cross the BBB so can be used in brain cancer therapy

Question 29

What are platinum coordinated complexes?

Answer 29

Cisplatin, carboplatin and oxaliplatin | Carboplatin is less toxic than cisplatin

Question 30

What do platinum coordinated complexes do?

Answer 30

From intra and inter strand crosslinks and interferes with DNA replication and transcription and therefore it acts in G1 and S phase

Question 31

What is oxiplatin used in?

Answer 31

Colorectal cancer

Question 32

What are the two topoisomerase I inhibitors?

Answer 32

Topotecan and irinotecan - S phase specific

Question 33

What can topotecan be used against?

Answer 33

Metastatic ovarian cancer and lung cancer

Question 34

What can irinotecan be used against?

Answer 34

Colorectal and rectal cancer alongside 5_FU & leucovorin

Question 35

What is the active form of irinotecan?

Answer 35

SN-38 - metabolised in cancer cells to form the active component

Question 36

How do irinotecan and topotecan work?

Answer 36

Prevent ligation following topoisomerase cleavage | Bind to the enzyme-DNA duplex

Question 37

How are topoisomerase I inhibitors administered?

Answer 37

Through IV and excreted in urine

Question 38

What is a problem with topotecan?

Answer 38

Myelosuppression

Question 39

What are topoisomerase II inhibitors?

Answer 39

Daunorubicin and doxorubicin - intercalate into DNA | Etoposide and teniposide - bind to transient cleavable form of enzyme-DNA complex leading to double strand breaks

Question 40

What are telomerase inhibitors?

Answer 40

Imetelstat - direct enzyme inhibitors | Modify oligonucleotides

Question 41

When do vinca alkaloids target cells?

Answer 41

Mitosis

Question 42

What do taxanes do?

Answer 42

Block mitosis in metaphase by binding to tubulin and inhibiting its polymerisation and stability of microtubules Induce spindle dysfunction

Question 43

When are taxanes active?

Answer 43

G2/M phase

Question 44

What are taxanes used to treat?

Answer 44

Ovarian cancer and breast cancers as well as non-small cell lung cancer

Question 45

What are the two vinca alkaloids?

Answer 45

Vincristine and vinblastine

Question 46

Are vinca alkaloids neurotoxic?

Answer 46

Yes

Question 47

Where is telomerase active?

Answer 47

Stem cells

Question 48

Where is telomerase inactive?

Answer 48

Somatic cells

Question 49

What is Etoposide used in combination with for testicular cancer?

Answer 49

Bleomycin & cisplatin

Question 50

What does teniposide treat?

Answer 50

Glinomas and neuroblastomas

Question 51

Can alkylating agents be used in brain cancer?

Answer 51

Yes - they are oral bioavailable and cross the BBB

Question 52

What does topoisomerase do?

Answer 52

Reversible single-stranded breaks in the DNA a duplex which act to relieve torsional strain

Question 53

Where do platinum coordinated complexes metabolites go to?

Answer 53

The urine - poor penetration into the CNS