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Pharmacology 3001 > Cancer Chemotherapy > Flashcards

Cancer Chemotherapy Flashcards

1
Q

What are the 3 main approaches to dealing with established cancers?

A
  • Surgical excision
  • Radiotherapy
  • Chemotherapy
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2
Q

What are the 4 main types of traditional chemotherapy agents?

A
  • Alkylating agents
  • Antimetabolites
  • Cytotoxic antibiotics
  • Plant derivatives
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3
Q

What is the mechanism of action of alkylating agents?

A
  • They form covalent bonds with suitable nucleophilic substances
  • They cause intrastrand cross-linking of DNA which causes knock on effects to then kill the cancer cells
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4
Q

WHat are the 6 major groups of alkylating agents?

A
  • Nitrogen mustards
  • Ethylenimines
  • Alkylsulphonates
  • Hydriazines and triazine s
  • Nitrosoureas
  • Platinum based compounds
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5
Q

Give an exmaple of a nitrogen mustard

A

Cyclophosphamide

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6
Q

Give an example of an Ethylenimine

A

Thiotepa

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7
Q

Give an example of an alkylsulphonate

A

Busulphan

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8
Q

Give an example of a hydrazine/triazine

A

Temozolomide

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9
Q

Give an example of a nitrosoureas

A

lomusine or carmustine

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10
Q

Give an example of a platinum based compound

A

Cisplatin

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11
Q

What are antimetabolites?

A

Look like normal natural molecules so are taken up by cells but when they are taken up by cancer cells they mess up the metabolic pathway

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12
Q

What are the 3 main groups of antimetabolites?

A
  • Antifolates
  • Antipyrimidines
  • Antipurines
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13
Q

Give an example of a commonly prescribed antifolate

A

Methotrexate

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14
Q

Give an example of an antipyrimidine

A

5-FU or gemcitabine

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15
Q

Give an example of an antipurine

A

Mercaptopurine or thioguanine

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16
Q

What are the 4 main types of cytotoxic antibiotics?

A
  • Anthracyclines
  • Dactinomycin
  • Bleomycin
  • Mitomycin
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17
Q

Give an example of an anthracycline

A

Doxorubicin

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18
Q

What are the two main mechanisms of action of plant derivatives?

A
  • Spindle poisons - inhibit microtubule function during metaphase
  • Topoisomerase inhibitors (type 1 or 2) to do with the unwinding of the DNA helix
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19
Q

What are the 2 main types of spindle poisons (plant derivatives)?

A
  • Vinca alkaloids

- Taxanes

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20
Q

Name vinca alkaloid drug

A

Vincristine, vinblastine

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21
Q

Name a taxane drug

A
  • Paclitaxcel (taxol)

- Docetaxel

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22
Q

What are the two types of topoisomerase inhibitor (plant derivative)?

A
  • Camptothecins (top 1)

- Etoposide (top 2)

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23
Q

Name a camptothecin drug

A

Irinotecan

24
Q

What are the main drawbacks of chempotherapy of cancer?

A
  • Target cell proliferation not the more lethal properties of invasiveness and metastasis
  • Non-specific cell killlers rather than being aimed at the particular changes which maje a cell malignant
  • The development of resistance (particularly multidrug resistance) to anticancer drugs
  • ## Leaves some remaining cells
25
Q

What kind of cells are often affected by chemotherapy drugs?

A
  • Bone marrow
  • GI
  • Hair
  • Skin
  • Mucosa
26
Q

What side-effect can anthracyclins cause?

A

Cardiotoxicity

27
Q

What side-effect can vinca alkaloids cause?

A

Neuropathy

28
Q

What is a specific side-effect of high dose cisplatin?

A

Ototoxicity (ear problems)

29
Q

What is Tumour-Lysis syndrome?

A
  • An acute side-effect and a metabolic emergency
  • Occurs due to rapid cell lysis (death) and large amounts of cell metabolites in blood
  • If untreated can lead to acute renal failure, CA and death
30
Q

What does tumour lysis syndrome show in the blood (in terms of metabolites)?

A
  • Hyperuricaemia
  • Hyperphosphataemia
  • Hyperkalaemia
  • Hypocalcaemia
31
Q

What property of human cells makes them more affected by chemotherapy?

A

Shorter life-span

32
Q

What does emetogenic mean?

A

Causing nause and vomitting

33
Q

What chemotherapy drug can cause especially high emetogenic affects?

A

Cisplatin

34
Q

What specific side-effects can chemotherapy cause to the GI system?

A
  • Nausea
  • Vomitiing
  • Diarrhoea
  • Constipation
  • Loss of appetite
  • Ulceration, dry mouth pain, taste alterations
35
Q

What monoclonal antibody is used against B cell lymphomas and targets a specific B cell surface protein?

A

Rituximab

36
Q

What monoclonal antibody is used against breast cancer?

A

Trastuzumab

37
Q

What receptor does trastuzamab target?

A

Epidermal growth factor receptor 2 (HER2/ERBB2)

38
Q

What drug is used against CML?

A

Imatinib

39
Q

What gene-signalling pathway soes imatinib specifically inhibit?

A

bcr-abl gene signalling pathways

40
Q

What factors does personalised medicine take into account when prescribing a drug for cancer?

A
  • Family history
  • Socioeconomic circumstances
  • Enviromental
  • Genomic/genetic testing
  • Proteomic profiling
  • Metabolomic analysis (study metabolites)
41
Q

What are the 4 Ps of Personalised Medicine?

A
  • Predictive
  • Personalised
  • Preventative
  • Participatory
42
Q

What are the aims of stratified medicine?

A
  • Improved prevention based on underlying predisposition
  • Earlier diagnosis of disease as a result of identifying abnormality earlier
  • More precise diagnosis based on cause and
  • Targeted interventions through the use of companion diagnostics to identify and stratify patients for effective treatment
43
Q

What drug is used to treat non small cell lung cancer (EGFR mutation)?

A

Erlotinib

44
Q

Would erlotinib be used in a NSCLC involving a KRAS mutation?

A

No

45
Q

What drug would be used in a NSCLC involving an ALK rearrangment?

A

Crizotinib

46
Q

What monoclonal antibody would be used in the treatment of colorectal cancer?

A

Cetuximab

47
Q

When would cetuximab not be used in the treatment of colorectal cancer?

A

If a RAS mutation was present (KRAS/NRAS mutation)

48
Q

When would Vermurafenib be used?

A

Melanoma (with a BRAF-activating mutation)

Roughly 40 - 60% of melanomas

49
Q

What drug would be used for a melanoma with an NRAS mutation?

A

MEK inhibitors / combinations

50
Q

When would imatinib be used?

A
  • CML

- OR KIT mutations (3% of melanomas)

51
Q

What drug is used to repair DNA after chemotherpy?

A

MGMT

52
Q

What can FISH (fluorescent in situ hybridisation) be used for?

A

Diagnosis of cancer (can be used to determine what specific type)

53
Q

What is nivolumab?

A
  • Fully human IgG4 PD-1 immune-chechpoint-inhibitor antibody that disrupts PD-1-mediated signaling
  • Restores antitumour immunity
54
Q

What is checkpoint inhibitor therapy?

A

Reactivates immune system to see cancer cells

55
Q

What monoclonal antibody is used in metastic melanomas (it is an anti-CTLA-4 antibody)?

A

Ipilimumab

56
Q

What are PD-1 and PD-L1?

A
  • PD-1 is found on T cells and acts as on ‘off switch’ that helps keep other T cells from attacking other cells in the body
  • PD-1 attaches to PD‑L1, a protein found on some normal (and cancer) cells
  • This interaction basically tells the cell to not attack the other cells
  • Prevents auto-immune disease
  • PD-1 = receptor PDL-1 = ligand

Pharmacology 3001 (13 decks)

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