3 - chemotherapy Flashcards

(52 cards)

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
cyclophosphamide activation and bioavailabiliry
high bioavailability orally and IV | activated by hepatic enzymes into toxic acrolein and phosphoramide mustard
26
what is cisplatin
platinum analogue | alkylating agent
27
what do platinum analogues cause
lead to inter-strand crosslinks leading to inhibition of DNA synthesis and function (alkylating agent, but different structure)
28
what is the role of folic acid
provides methyl groups for the synthesis of precursors of DNA and RNA (thymine or uracil)
29
what is folic acid converted into and how
reduced to FH4 cofactors
30
how do folic acid analogues work
interfere with FH4 metabolism thereby inhibiting DNA replication
31
what is methotrexate
folic acid analogue that binds with high affinity to the active catalytic site of dihydrofolate reductase
32
when is methotrexate most effective
during S phase and when they are proliferating rapidly
33
where do vinca alkaloids come from
periwinkle plant
34
what is the mechanism of action of vinca alkaloids
inhibit tubulin polymerization | M phase
35
where do taxanes come from
pacific yew tree
36
what is the mechanism of action of taxanes
promote microtubule assembly through high affinity binding M phase inhibition (you need to build them up and break them down)
37
what are DNA topoisomerases
nuclear enzymes that reduce torsional stress in supercoiled DNA (through strand breaking and reassembly)
38
what is the mechanism of action of camptothecins
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
how do camptothecins cause single stranded breaks in DNA
bind and stabilize the DNA-topoisomerase 1 which leads to a prevention of re-ligation (initial cleavage not affected)
40
which phase do camptothecins affect
S phase
41
how do anthracyclines work (4 things)
inhibit topoisomerase generate free radicals high binding affinity to DNA bind cellular membrane to alter fluidity and ion transport
42
how do the streptomyces antibiotics work
bind DNA through intercalation, block DNA synthesis and cell replication
43
what is imantinib
tyrosine kinase inhibitors
44
how does imantinib work
inhibits the tyrosine kinase domain of the BCR-ABL oncoprotein (philly)
45
what is imantinib good for
good for leukemia
46
what does activation of epidermal growth factor receptor (EGFR) cause
promotes cell growth and proliferation, invasion, metastasis and angiogenesis
47
what is cetuximab and what does it do
monoclonal antibody directed agains EGFR (epidermal growth factor receptor)
48
what is tamoxifen
selective estrogen receptor antagonist
49
how does tamoxifen work and what is it used for
blocking binding of estrogen to estrogen sensitive cancer cells in breast tissue
50
what is primary resistance to chemo drugs
spontaneous mutation in absence of prior exposure to anti-cancer drugs (like p53 mutations)
51
what is acquired resistance to chemo drugs
develops in response to a given anticancer agent (like a p-glyco pump that develops)
52
which base pair does cyclophosphamide crosslink
guanine-guanine