3 - chemotherapy Flashcards

1
Q

what are the 5 stages of the cell cycle

A

G1 S G2 M G0 (quiescent)

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2
Q

where are the checkpoints in the cell cycle

A

G1 and G2 (ready for synthesis and ready for mitosis)

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3
Q

what are the two types of genes that regulate the cell cycle

A

tumor suppressor genes and oncogenes

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4
Q

what are the 3 main roles of tumor suppressor genes

A

inhibit cell division
initiate apoptosis following irreversible DNA damage
DNA repair proteins

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5
Q

what is p53

A

tumor supressor protein that regulates cell cycle

mutated in 50% of all tumors

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6
Q

what are proto-oncogenes

A

normal genes involved cell growth and proliferation, or

inhibit apoptosis

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7
Q

what are point mutations

A

small scale deletions or insertions

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8
Q

what are chromosomal translocations

A

when two separate chromosomal regions become abnormally fused

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9
Q

what is a Philadelphia chromosome (structure)

A

chromosome 22 with BCR gene fused to 9 with ABL 1 gene (makes tyrosine kinase)

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10
Q

what happens when you have a Philadelphia chromosome

A

unregulated expression of protein tyrosine kinase activity leading to unregulated cell cycle and division
found in leukaemia cancer cells

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11
Q

what kind of mutations and how many are needed to make cancer

A

multiple oncogenes and mutated tumor suppressor genes

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12
Q

which phases are tumor cells more susceptible to anti cancer drugs and why

A

S and M because they have more proliferating cells

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13
Q

what do pyrimidine analogyes do

A

compete with pyrimidine precursors for the enzyme thymidylate synthase (TS)

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14
Q

what is thymidylate synthase (TS) required for

A

the converson of dUMP to dTMP

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15
Q

what is 5-fluorouracil

A

a pyrimidine analogue

5-FU

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16
Q

is 5-fluorouracil active in its parent form

A

no

needs to become the active metabolite FdUMP

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17
Q

what is 6-mercaptopurine

A

purine analogue

inhibits purine nucleotide biosynthesis

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18
Q

how do purine analogues work

A

inhibit phophoribosyl pyrophosphate amidotransferase

rate limiting factor for purine synthesis

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19
Q

what are alkylating agents

A

highly reactive compounds which covalently link to chemicl groups commonly found in nucleic acids (amine, phosphates, sulfhydryl, OH)

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20
Q

what do alkylating agents cause

A

cross linking between strands of DNA and strand breakage

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21
Q

which specific nucleotide (and number) is susceptible to the formation of covalent bond with alkylating agents

what bond is formed?

A

N7 atom of guanine

G-G crosslink

22
Q

what is so special about the N7 atom of guanine

A

it is particularly susceptible to the formation of covalent bond with alkylating agents

23
Q

which stages of the cell cycle are most sensitive to alkylating agents

A

late G1 and S

24
Q

what is cyclophosphamide

A

alkylating agent

25
Q

cyclophosphamide activation and bioavailabiliry

A

high bioavailability orally and IV

activated by hepatic enzymes into toxic acrolein and phosphoramide mustard

26
Q

what is cisplatin

A

platinum analogue

alkylating agent

27
Q

what do platinum analogues cause

A

lead to inter-strand crosslinks leading to inhibition of DNA synthesis and function (alkylating agent, but different structure)

28
Q

what is the role of folic acid

A

provides methyl groups for the synthesis of precursors of DNA and RNA (thymine or uracil)

29
Q

what is folic acid converted into and how

A

reduced to FH4 cofactors

30
Q

how do folic acid analogues work

A

interfere with FH4 metabolism thereby inhibiting DNA replication

31
Q

what is methotrexate

A

folic acid analogue that binds with high affinity to the active catalytic site of dihydrofolate reductase

32
Q

when is methotrexate most effective

A

during S phase and when they are proliferating rapidly

33
Q

where do vinca alkaloids come from

A

periwinkle plant

34
Q

what is the mechanism of action of vinca alkaloids

A

inhibit tubulin polymerization

M phase

35
Q

where do taxanes come from

A

pacific yew tree

36
Q

what is the mechanism of action of taxanes

A

promote microtubule assembly through high affinity binding
M phase inhibition
(you need to build them up and break them down)

37
Q

what are DNA topoisomerases

A

nuclear enzymes that reduce torsional stress in supercoiled DNA (through strand breaking and reassembly)

38
Q

what is the mechanism of action of camptothecins

A

bind and stabilize the DNA-topoisomerase 1 which leads to a prevention of re-ligation (initial cleavage not affected)
leads to an accumulation of single-stranded breaks in DNA

39
Q

how do camptothecins cause single stranded breaks in DNA

A

bind and stabilize the DNA-topoisomerase 1 which leads to a prevention of re-ligation (initial cleavage not affected)

40
Q

which phase do camptothecins affect

A

S phase

41
Q

how do anthracyclines work (4 things)

A

inhibit topoisomerase
generate free radicals
high binding affinity to DNA
bind cellular membrane to alter fluidity and ion transport

42
Q

how do the streptomyces antibiotics work

A

bind DNA through intercalation, block DNA synthesis and cell replication

43
Q

what is imantinib

A

tyrosine kinase inhibitors

44
Q

how does imantinib work

A

inhibits the tyrosine kinase domain of the BCR-ABL oncoprotein (philly)

45
Q

what is imantinib good for

A

good for leukemia

46
Q

what does activation of epidermal growth factor receptor (EGFR) cause

A

promotes cell growth and proliferation, invasion, metastasis and angiogenesis

47
Q

what is cetuximab and what does it do

A

monoclonal antibody directed agains EGFR (epidermal growth factor receptor)

48
Q

what is tamoxifen

A

selective estrogen receptor antagonist

49
Q

how does tamoxifen work and what is it used for

A

blocking binding of estrogen to estrogen sensitive cancer cells in breast tissue

50
Q

what is primary resistance to chemo drugs

A

spontaneous mutation in absence of prior exposure to anti-cancer drugs (like p53 mutations)

51
Q

what is acquired resistance to chemo drugs

A

develops in response to a given anticancer agent (like a p-glyco pump that develops)

52
Q

which base pair does cyclophosphamide crosslink

A

guanine-guanine