Cancer 4: Principles of Treatment

Question 1

give an example of an alkylating agent

Answer 1

chlorambucil

Question 2

List 6 different types of chemotactic drugs

Answer 2

1. Alkylating agents
2. Antimetabolites
3. mitotic inhibitors
4. antibiotics
5. agents that inhibit DNA synthesis
6. differentiation agents
7. horomones and hormone antagonists
8. dna topoisomerase I/II inhibitors
9. agents that inhibit DNA repair
10. inhibitors of DNA methylation

Question 3

which cells of the bodt are most at risk due to the narrow therapeutic index of chemo?

Answer 3

The therapeutic index for cancer chemotherapeutic agents is usually low and the cells of the bone marrow and the gastrointestinal tract are usually the most sensitive normal cells.

Question 4

list some side effects of chemo

Answer 4

Pain 
hair loss 
mouth sores 
trouble breathing 
N+V
weakened immune system 
bruising and bleeding 
neuropathy 
rashes 
Constipation/ diarrhea

Question 5

List some drugs that cause toxicity

Answer 5

nitrogen mustard 
vincristine 
procarbazine 
cyclophosphamide 
chlorambucil 
cisplatin

Question 6

How does rituximab work?

Answer 6

monoclonal antibody which binds to CD20 causing formation of MAC and destroying the cell as well as attracting macrophages to destroy the cell and attracting NK cells.

Question 7

how to targeted antibodies such as ofatumumab work?

Answer 7

they act as complement to cause complement mediated lysis, and have direct effects too.

Question 8

what does BCRABL do ?

Answer 8

A single molecular abnormality that causes transformation of a haematopoietic progenitor into a malignant clone

Question 9

why has there been resistacne to imatinib?

Answer 9

ABL kinase domain mutations
Increased amplification of BCR-ABL1
Clonal evolution (less reliance on BCR-ABL)
Drug efflux mechanisms (Imatinib is a P-gp substrate)

Question 10

how does vemurafinib work in melanoma patients?

Answer 10

Interrupts B-Raf/MEK/ERK pathway

Question 11

what is the MOA of ibrutinib ?

Answer 11

Bruton’s tyrosine kinase (BTK) inhibitor

Question 12

how can angiogenesis be targeted?

Answer 12

bevacizumab binds to VEGF to inhibit angiogenesis.

Question 13

how can we use the immune system to fight cancer?

Answer 13

1) cancer vaccines

2) blockade of checkpoint molecules

Question 14

how does checkpoint blockade work?

Answer 14

anti-CTLA4 antibody blocks CTLA4 and prevents inhibitory signals.
Blocking inhibitory receptors induces tumour regression

Question 15

how are CAR T cells used in patients.

Answer 15

take patients blood, culture with anti-CD3 and anti-CD28 and IL2 and transduce with CAR gene then transfer back into patient.

Question 16

what are the limitations to CART therapy?

Answer 16

1) cytokine storm
2) unclear how it works against solid tumour
3) will tumour develop resistance ?
4) has to be modified for each patient.
5) exhaustion of transferred T cells.
6) increased risk of autoimmune reaction