Lecture 7.3 Cancer Pharmacology Part 2

Question 1

What is the mechanism of action of chemo drugs on group 2?

Answer 1

Damage the DNA

Question 2

Which drug categories fall under group 2 chemo drugs?

Answer 2

• Alkylating agents
• Cytotoxic antibiotics
• Topoisomerase inhibitors (plant products)

Question 3

Which drugs fall under alkylating agents category?
What is their mechanism of action?

Answer 3

• Cyclophosphamide
• Busulfan
• Chlorambucil
• They Alkylate DNA, Cross-link DNA-DNA, Mispairing of bases, Depurination, trigger apoptosis

Question 4

Which drugs fall under the cytotoxic antibiotics category?

Answer 4

1. Antracyclines (Daunorubicin , doxorubicin, epirubicin, idarubicin)

These drugs cause cardiac toxicity, which can either be acute (arrhythmias) or chronic (cardiomyopathy)

MOA: intercalate, free radicals & inhibit DNA topoisomerase

2. Dactinomycin:
   MOA: intercalate, block DNA transcription, inhibit topoisomerase I & II

-light sensitive, avoid extravasation, GIT tox

3. Bleomycin:
   MOA: Oxidative damage to thymidylate, free radical formation, cutting of DNA backbone (phosphodiester linkages)

Adverse Reactions: anaphylactoid reactions, hyper-pigmentation , hyper-keratosis,

• lungs - fibrosis, no myelosuppression (bleomycin lung)

Question 5

3 effects resulting from topoisomerase inhibitors

Answer 5

• Ligation reaction inhibited
• Cause DNA strand breaks
• Prevent DNA copying

Question 6

Which Chemo drugs fall under topoisomerase inhibitor category?

Answer 6

• Podophyllotoxins (inhibit topoisomerase II)
  -etoposide- causes drug induced leukaemia
  -tenoposide- N&V, alopecia, myelosuppression
• Camptothecins (inhibit toposiomerase I)
  -topotecan, irinotecan (active metabolite = SN38)

 Mild AE profile; myelosuppression
 Irinotecan- dose limiting tox = severe diarrhoea

Question 7

Class 3 Chemo drugs are called

Answer 7

Miscellaneous drug targets in leukaemia

Question 8

4 chem drugs that fall under the Miscellaneous drug targets (grp 3 Chem drugs)

Answer 8

• Microtubule inhibitors (MOA: Inhibit mitosis)
• Kinase inhibitors
• Monoclonal antibodies
• Immune checkpoint inhibitors

Question 9

Chem drugs under microtubule inhibitors? What are their mechanism of action?

Answer 9

These drugs are called spindle poisons and platinum containing compound

1. Vinca alkaloids:

binds β tubulin – prevents
binding with α-tubulin, no microtubule formation
 NB! Vincristine, vinblastine

Vincristine is known to have a very low incidence of bone marrow suppression

2. Taxanes:

Cause aberrant polymerisation of the microtubules,
prevent depolymerisation
 Paclitaxel, docetaxel

ADR: Peripheral neuropathy
common for both agents

Question 10

What are kinases?

Answer 10

Stuff produces by cancer cells. Oncogenes code for kinases.

Question 11

What drugs inhibit kinases?

Answer 11

imatinib

Question 12

The first tryosine kinase inhibitor

Answer 12

Imatinib

Question 13

List the therapeutic uses of imatinib

Answer 13

 CML (BCR-ABL)
 GIST (KIT mutation)
 CMML (EVT6 –
PDGFR

Question 14

What are the adverse effects of Imatinib?

Answer 14

• Myelosuppression
• Congestive heart failure
• Cardiac failure
• Oedema

Question 15

4 chemo drugs that identify as monoclonal antibodies

Answer 15

THEIR MOA: Monoclonal antibodies bind and inhibit cell surface receptors
 Inhibits the effect of receptor stimulation
 Stimulate the immune system to target and destroy the cells
occupied by the antibody  complement system, ADCC

DRUGS:
- Rituximab binds to CD20 protein on lymphocytes
 Alemtuzumab binds to CD52 protein on immune cells
 Cetuximab binds and blocks the EGFR and EGFR signalling
 Ipilimumab binds to the CTLA-4 receptor and prevents the
downregulation of T-cell activation

Question 16

Mechanisms of McAB killing of cancer cells

Answer 16

1. Direct tumour cell killing
2. Immune-mediated tumour cell killing
3. Vascular and stromal cell ablation