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MEDSCI302 > 31 History of Cancer Drugs > Flashcards

31 History of Cancer Drugs Flashcards

1
Q

2 general classes of cancer drugs developed

A

ChemoTx

Single-molecule targeted Tx

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2
Q

Limitation of chemoTx?

A

Targets rapidly-proliferating cells

= lacks SPECIFICITY (side effects)

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3
Q

Name the 2 early scientists who had early approaches to cancer Tx
What did they discover?

A

Coley - gram +/- bac for lymphoma + sarcoma (immuneTx)

Beatson - Oophorectomy for breast cancer patients (lead to Tamoxifen for ER+ tumors)

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4
Q

Name the 5 classes of cytotoxic drugs (acronym)

A 
AAPTM
Antimetabolites
Alkylating drugs
Platinating drugs
Topoisomerase poisons - CPT, Etopiside, Doxorubicin
Mitotic poisons
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5
Q

How were Alkylating drugs discovered

A

Accidental release of MUSTARD GAS caused immunosuppression

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6
Q

Examples of alkylating drugs

A 
Cyclophosphamide (interstrand x-links)
Nitrogen mustard (interstrand x-links)
TMZ + Dacarbazine (methylating)
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7
Q

Concept of antimetabolities?

A

MIMIC metabolites = block ENZYMES

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8
Q

2 types of antimetabolites?

What do they block?

A 
Folic acid (MTX) - blocks DHFR (depletes dTMP = block DNA synthesis)
Nucleic acid ANALOGS - incorporate into DNA directly to cause stress signal
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9
Q

Give examples of nucleic acid analogs (antimetabolites0

A

5-FU
6-mercaptopurine
Ara-C (Cytosine analogs)

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10
Q

Examples of ANTIBIOTICS that interact directly with DNA?

A

Topoisomerase poisons

  • Doxorubicin
  • Daunorubicin
  • Actinomycin D
  • Mitomycin D
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11
Q

How do MITOTIC poisons work?

Examples?

A

Bind b-subunit of tubulin to disrupt MTs

eg. Alkaloids (Vinblastine, Vincristine)

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12
Q

Name 3 plant products and the plant they come from

A

Paclitaxel - Yew tree
Etopisides - Mandrake root toxic
Camptothecin - Camptotheca tree

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13
Q

Name a SYNTHETIC compound and its MoA

A

Cisplatin = forms INTRAstrand x-links to block CC

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14
Q

What was a major LIMITATION for early drug screening?

A

Lack of effective screening MODELS

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15
Q

Name the 3 classes of MODELS developed

A

Tumor models
Cell cultures
NCI testing program

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16
Q

Advantages of transplantable TUMOR models

A
  • Standardisation of models

* Screening MANY compounds at once

17
Q

Example of a tumor transplant model?

A

Nude mice - immunodeficient

18
Q

Limitations of mice models

A

Unethical
Species differences (lack some targets)
Expensive

19
Q

Advantages of CELL CULTURES

A

HUMAN cell lines = species-specific
96-well technology = HIGH throughput analysis
Commercially available cell lines

20
Q

How does NCI testing work?

A

Candidate drugs screened against a PANEL of 60 cell lines
= FINGERPRINT of IC50 values obtained
= look for drugs with UNIQUE fingerprints (new Tx?)

21
Q

Advantages of NCI testing?

A
  • Standardisation
  • High-throughput analysis
  • NEW Tx
22
Q

ADVANTAGES of molecularly-targeted Tx

A

SPECIFICITY improved (exploits genetic abnormalies and signalling pathways of tumor cells)

23
Q

What technique is particularly useful for KINASES?

Why?

A

Molecular modelling (kinases have a BINDING-POCKET)

24
Q

Give 4 examples of molecularly-targeted Tx

A 
HIRG
Herceptin
Rressa
Rituximab
Gleevac
25
Q

What is Rituximab?

What cancer does it target?

A

Chimeric monoclonal antibody, targets B-cell antigen CD20 (kills MATURE cells only, naive B-cells don’t exp CD20)
= non-Hodgkin’s Lymphoma

26
Q

What is Herceptin?

What cancer does it target?

A

Humanised recombinant monoclonal antibody
Targets HER2 (part of EGFR heterodimer)
= present in ~30% breast cancers

27
Q

What is Iressa?

What cancer does it target?

A

Inhibits RTK activity of EGFRs

= breast, ovarian, lung cancers

28
Q

What is Gleevac?

What cancer does it target?

A

100% selective for Bcr-Abl fusion protein

= CML, GI stromal tumors

29
Q

2 classes of VASCULAR targetting drugs

Differences between them?

A

Anti-ANGIOGENIC - blocks growth of NEW BVs

Anti-VASCULAR - acts on MATURE BVs

30
Q

Downstream effects of anti-VASCULAR agents on the tumor?

A

Disrupt BF = induce hypoxia + necrosis of tumor

31
Q

Give an example drug for:
Anti-angiogenic
Anti-vascular

A

Avastin (anti-angiogenic)

DMXAA (anti-vascular)

32
Q

What is Avastin?

What cancer does it target?

A

Humanised monoclonal antibody, inhibits VEGF (anti-angiogenic drug)
= CRC (in combo with 5-FU)

33
Q

What is DMXAA

A

Anti-vascular drug
= EC dmg/apoptosis
= vasoPERM
= disrupt tumor BF

= tumor HYPOXIA + NECROSIS

MEDSCI302 (8 decks)

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