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Cancer > Chemotherapy > Flashcards

Chemotherapy Flashcards

1
Q

How can chemotherapeutic drug be classified?

A

Classification I:
Cell cycle specific vs Cell cycle non-specific

Classification II:

  1. Directly acting cytotoxic drugs:
    - alkylating agents
    - antimetabolites
    - natural products
    - miscellaneous
  2. Indirectly acting drugs:
    - corticosteroids
    - oestrogen + ERMs
    - 5-alpha reductase inhibitors
    - GNRH agonists
    - Progestins
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2
Q

Give examples of cell cycle NON specific chemo drugs.

A 
Cyclophosphamide 
Chlorambucil 
Cisplatin 
Actinomycin-D
L-asparaginase
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3
Q

How does Cyclophosphamide work?

A

Main effects due to its metabolic phosphoramide mustard
forms irreversible DNA cross-links
leads to cell apoptosis

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4
Q

How does Chlorambucil work?

A

Alkylating agent/nitrogen mustard
Produces its anti-cancer effects by interfering with DNA replication and damaging the DNA within cells (cross-linking, adding alkyl groups to bases, mutations)
Damage to DNA induces cell cycle arrest and cellular apoptosis
(accumulation of p53 and activation of BCL2)

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5
Q

How does Cisplatin work?

A

Cross-links DNA (especially purine bases) and interferes with mitosis
causes cellular apoptosis

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6
Q

How does Actinomycin-D work?

A

Inhibits transcription by binding DNA at the transcription initiation complex and preventing elongation of RNA chain by RNA polymerase

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7
Q

How does L-asparaginase work?

A

converts l-asparagine to aspartic acid and ammonia
deprives cancerous cells of circulating l-asparagine leading to cell death (as cancer cells cannot synthesis asparagine on their own)

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8
Q

Give examples of chemo drug(s) that block G1 phase in the cell cycle.

A

Vinblastine

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9
Q

Give examples of chemo drug(s) that block S phase in the cell cycle.

A

MTX
6-Mercaptopurine
5-Fluorouracil

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10
Q

Give examples of chemo drug(s) that block G2 phase in the cell cycle.

A

Bleomycin
Etoposide
Topotecan
Daunorubicin

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11
Q

Give examples of chemo drug(s) that block M phase in the cell cycle.

A

Vincristine
Vinblastine
Paclitaxel
Docetaxel

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12
Q

How do alkylating agents work as chemotherapeutic drugs?

A

Crosslink guanine nucleobases in DNA double helix strands
strands are unable to coil and separate
this is necessary in DNA replication, therefore the cells can no longer divide

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13
Q

Give examples of alkylating agents.

A
  • Nitrogen mustards: meclorethamine, melphalan, chlorambucil, cyclophosphamide, ifosfamide
  • Ethyleneimine: thiotepa
  • Alkyl sulfonate: Busulfan
  • Nitrosureas: carmustine, lomustine, streptozocin
  • Triazine: dacarbazine, temozolamide
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14
Q

How do antimetabolites works as chemotherapeutic drugs?

A

Interfere with DNA production and therefore cell division and tumour growth
Either (1) become a part of the DNA and block S phase in the cell cycle OR (2) interfere with RNA synthesis

Also inhibits thymidine synthesis via thymidylate synthase and therefore selectively inhibits DNA synthesis

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15
Q

Give examples of antimetabolite drugs.

A
  • Folate antagonists: MTX
  • Purine antagonists: 6-Mercaptopurine, 6-hioguanine, Azathioprine
  • Pyrimidine antagonists: 5-Fluorouracil, Cytarabine, gemcitabine
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16
Q

Give examples of natural products used in chemotherapy.

A
  • antibiotics
  • vinca alkaloids
  • taxanes
  • enzymes (l-asparaginase)
  • epipodophyllotoxins
  • camptothecin analogs
  • biological response modifiers
17
Q

List antibiotics used as chemotherapy.

A 
actinomycin D
doxorubicin 
bleomycin 
daunorubicin 
mitomycin C
18
Q

How do vinca alkaloids work? List examples of vinca alkaloids.

A

Anti-mitotic and anti-microtubule agents
act upon tubulin and prevent it from forming into microtubules –> prevent microtubule polymerisation
this is necessary for cell division, therefore it stops cells growth
prevent mitotic spindle formation

Examples:

  • vincristine
  • vinblastine
  • vinorelbine
19
Q

How do taxanes work as chemotherapy? list examples of taxanes.

A

Disrupt microtubule function
Stabilise the GDP-bound tubulin
Inhibit cell division as Depolymerisation is prevented

Examples:

  • paclitaxel
  • docetaxel
20
Q

What are epipodophyllotoxins? Give examples.

A

They inhibit topoisomerase II

Examples:
1. Etoposide: prevents re-ligation of DNA strands and therefore causes DNA to break –> error in DNA synthesis = apoptosis

  1. Teniposide: inhibition of topoisomerase II (prevent DNA from unwinding)
21
Q

What is Topotecan? What is its MOA?

A

A camptothecin analog
prevents topoisomerase I from re-ligating DNA
the trapped topoisomerase-I complexes accumulation to stimulate apoptosis
disruption also prevents DNA replication and causes cell death

22
Q

What is Irinotecan? What is its MOA?

A

A camptothecin analog

Inhibits topoisomerase I via active metabolite (SN-38) and therefore prevents DNA replication and transcription

23
Q

Give examples of biological response modifiers.

A

Interferons and interleukins

24
Q

Give an example of a corticosteroid that can be used as a chemotherapeutic drug.

A

Prednisolone

can bind to glucocorticoids response elements and therefore can enhance or inhibit gene expression

25
Q

Why can ethinyl estradiol be used as chemotherapy?

A

Oestrogens can have anti-androgen effects

therefore can suppress tumour growth

26
Q

What are Tamoxifene and Toremifene?

A

Selective oestrogen receptor modulators

27
Q

What is Fulvestrant? How does it work?

A

It is a selective oestrogen receptor degrader

It makes the receptor unstable and misfold - causes the normal processes inside the cell to degrade

28
Q

Give examples of aromatase inhibitors.

A

Letrozole
Anastrazole
Exemestane

*lower oestrogen production, which can suppress growth of hormone-sensitive cancerous cells

29
Q

Give an example of a progestin

A

Hydroxyprogesterone

30
Q

Give examples of anti-androgens

A

Flutamide

Bicalutamide

31
Q

How do 5-alpha reductase inhibitors work? Give examples.

A

5alpha reductase: reduces steroid double bound in testosterone to is more active form, dihydrotestosterone (DHT). Inhibiting the enzyme, reduces the active DHT present.

Examples:

  • Finasteride: selective inhibitor of the type II and type III isoforms of the enzyme
  • Dutasteride: inhibits all 3 isoforms of the enzyme
  • both are irreversible
32
Q

Give examples of GnRH analogs.

A

Naferelin
Goserelin
Leuoprolide

33
Q

How does carboplatin work?

A

Similar mechanism to cisplatin (aquation)
interferes with DNA (probably by cross linking)
This prevents mitosis and therefore cell/tumour growth

34
Q

How does hydroxyurea work?

A
  • AKA hydroxycarbamide
  • is a monohydroxyl-substituted urea (hydroxycarbamate) antimetabolite
  • acts by disrupting the DNA replication process
  • selectively inhibits ribonucleoside diphosphate reductase
  • the enzyme is required to convert ribonucleoside diphosphates into deoxyribonucleoside diphosphate
  • this prevents cells from leaving the G1/S phase of the cell cycle
35
Q

How does Mitotane work?

A

It is a cytostatic antineoplastic medication

*rarely used it is an inhibitor of the adrenal cortex –> used in adrenal cortical carcinoma

36
Q

How does Imatinib work?

A

Tyrosine kinase inhibitor
Constitutively active tyrosine kinase bcr-abl activity which increases certain pro-oncogenic pathways:
1. Ras/ MapK pathway (increase proliferation)
2. PI3K/Bcl-2 pathway (prevent apoptosis)
3. JAK/STAT pathway (increase proliferation)

Therefore imatinib prevents up regulation of these pathways
If bcr-abl tyrosine kinase cannot perform its anti-apoptotic functions it results in cell death

37
Q

Which types of cancer are chemo-resistant?

A
  1. NSCLC
  2. GI cancer
  3. Pancreatic cancer
  4. Melanoma
38
Q

List examples of complications associated with chemotherapy.

A 
Tiredness
Nausea + vomiting
Hair loss
Risk of infection requiring hospitalisation 
Infertility 
Long term secondary malignancies

Cancer (7 decks)

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