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The Public - Year 2 > Cancer > Flashcards

Cancer Flashcards

1
Q

What is the purpose of chemotherapy?

A

Prevent cell growth

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2
Q

How does chemotherapy target DNA?

A
  • indirect interaction with DNA

- prevention of nucleic acid synthesis by inhibiting one or more enzymes involved

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3
Q

Give examples of alkylating agents

A
  • Melphalan
  • Chlorambucil
  • Cyclophosphamide
  • Decarbazine
  • Bulsulfan
  • Temozolamide
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4
Q

How do mustards work?

A

Attack guanine in DNA, this causes cross linking of DAN strand - they can’t open and be copied for cell division.
Linkage inhibits DNA synthesis - has a cytotoxic effect

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5
Q

Which other cells are also affected by mustards?

A

Those that divide frequently - GIT, bone marrow, testicles and ovaries

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6
Q

What is the state of the nitrogen on chlorambucil?

A

nitrogen lone pair is delocalised

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7
Q

What does melphalan minis?

A

An amino acid - drug enters by phenylalanine amino acid transporter

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8
Q

What is mitomycin C

A

a pro-drug that requires reductive activation.

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9
Q

What do alkylating agents contain?

A

Highly electrophilic groups -

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10
Q

How do alkylating agents work?

A

They form covalent bonds to nucleophilic groups in DNA. They prevent replication and transcription

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11
Q

What can alkylation of nucleic acid bases lead to?

A

mutations which are carcinogenic

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12
Q

What do neutral inactive molecules act as?

A

Pro-drugs

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13
Q

What is platinum covalently linked to?

A

Chloro-substituents

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14
Q

Where are complexes activated?

A

In cells with low Cl- ion cocn

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15
Q

How does cisplatin work?

A

Binds to DNA regions rich with guanine units forming intra-strand links

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16
Q

What are the toxic side effects of cisplatin?

A
  • severe nausea and vomiting
  • nephrotoxicity
  • ototoxicity
  • bone marrow suppression
17
Q

What do hydration procedures do?

A

reduce side effects making it harder for drugs to activated in non-cancer cells

18
Q

What is given as anti-sickness medication?

A

Metoclopramide

19
Q

Give an example of an intercalating agent

A

Doxorubicin

20
Q

How do intercalating agents work?

A

Slide between stacked bases inserted between adjacent pairs - they are stabilised by electrostatic interactions between DNA phosphate groups and positively charged amino group of sugar moiety. This leads to inhibition of topo II and also generates O2 free radicals

21
Q

What are the side effects of intercalating agents?

A
  • nausea & vomiting
  • myelosuppresion
  • alopecia
  • cardiotoxicity
22
Q

How do DNA topoisomerases work?

A

They modify the topological state of DNA by inducing transient single strand or double strand - this leads to DNA breakage. This is essential for uncoiling of DNA for replication, transcription or recombination

23
Q

What do inhibitors of DNA topoisomerases do?

A

block the action of topoisomerase leading to permanent single strand or double strand break

24
Q

What is the purpose of topoisomerase 2?

A

It relieves strain in DNA by cleaving DNA chain and crossing an intact strand through the broken strand.
Tyr residues are involved in chain breaking and they form covalent bonds. The ends pull chains apart to create a gap and the intact strand of DNA is passed through

25
Q

How does Etopside work?

A

It forms a ternary complex with DNA and topoisomerase II, this prevents DNA re-ligation so the double strand breaks. It is effective in chemo-sensitive tumours.

26
Q

What are the side effects of Etopside?

A
  • myelosuppression
  • nausea and vomiting
  • hair loss
27
Q

How do antimetabolites work?

A
  • They interfere with production of nucleic acids.
  • Inhibit production of deoxyribonucleoside triphosphate, precursors of DNA synthesis
  • inhibit formation of normal precursors by completing for metabolic enzymes
28
Q

Which amino acids are antimetabolites structurally similar to?

A

purine and pyrimidine

29
Q

Give examples of antimetabolites

A

5-FU
Methotrexate
Gemcitabine

30
Q

What are vincristine and vinblastine used to treat?

A

Leukaemia and Hodgkins disease

31
Q

How do vincristine and vinblastine work?

A

They prevent polymerisation of microtubules

32
Q

What is taxol used to treat?

A

Lung, ovarian and breast cancer

Kaposi’s sarcome

33
Q

How does taxol work?

A

Binds and stabilises microtubules.

34
Q

What are the advantages of antisense therapy?

A
  • same effect as enzyme inhibitor or receptor antagonist
  • highly specific where oligonucleotide is 17 nucleotides or more
  • smaller dose levels required compared to inhibitors or antagonists
  • potentially less side effects
35
Q

What are the disadvantages of antisense therapy?

A
  • ‘exposed sections of mRNA must be targeted
  • instability and polarity of oligonucleotides
  • short life time of oligonucleotides and poor absorption across cell membranes.

The Public - Year 2 (9 decks)

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