Cancer

Question 1

What are the types of treatments used in cancer?

Answer 1

Surgery
Radio therapy
Targeted therapy
Chemotherapy

Question 2

What are the types of targeted therapies?

Answer 2

RNA targeted
Tyrosine kinase receptor targeted
Inflammation targeted

Question 3

Describe the types of RNA targeted therapy?

Answer 3

ANTISENSE
MOA:
1. DNA converted to mRNA
2. Antisense Oligonucleotide complementary to a section on mRNA
3. Binds and inhibits mRNA conversion to a protein

MICRO-RNA
MOA:
1. mi-RNA= short segments of dsRNA
2. Recognition by RISC enzyme complex
3. Becomes siRNA (small inhibitory) 
4. siRNA binds complementary mRNA
5. RISC cleaves mRNA= Degradation= no gene product synthesis

Question 4

What is signal transduction?

Answer 4

Transmittance of signal through a cell, from a cells exterior to interior.

Question 5

Describe the steps in signal transduction?

Answer 5

1. Ligand/protein bind to Receptor with high affinity
2. Conformational receptor change
3. Extracellular signals converted to intracellular signals

Question 6

Give an example of a signal transduction pathway?

Answer 6

MAPK signalling pathway

Question 7

Describe the structure of tyrosine kinase receptor involved in MAPK signalling pathway?

Answer 7

Extracellular domain= ligand binding site
Transmembrane domain= alpha helix
Cytosol domain= TKR activity
Intracellular domain= site of phosphorylation of Tyr residues on proteins

Question 8

Describe the steps in MAPK signalling pathway?

Answer 8

1. Ligands bind to adjacent tyrosine kinase receptors
2. Receptors associate and dimerise
3. Tyrosine kinase domains become activated
4. Tyrosine residue is phosphorylated in the intracellular domain
5. Phosphorylated group act as binding site for intracellular signalling protein
6. Leads to cascade and activation of downstream signalling pathways

Question 9

What cancer drugs target kinases and signal transduction pathway?

Answer 9

Bevacizumab
Trastuzumab 
Herceptin
Imatinib mesylate
Gefitinib
Tamoxifen
Dabrafenib
Vemurafenib

Question 10

What is the use and mode of action of Bevacizumab?

Answer 10

Colorectal cancer use
MOA: Disrupts ligand receptor binding
1. Bind to tumour protein VEGF
2. Inhibits VEGF binding to its receptors and blocks signal initiation
3. Inhibits cell proliferation and stops new blood vessels forming

Question 11

What is the use and mode of action of Trastuzumab and Herceptin?

Answer 11

Over expressed HER2 tumours
MOA: Disrupts ligand receptor binding
1. Binds to EGF
2. Prevents HER 2 receptor and EGF binding
3. Blocks signal transduction

Question 12

What is the use and mode of action of Imatinib mesylate?

Answer 12

Chronic myeloid leukemia
Acute lymphoblastic leukemia
Intestinal stromal tumours
MOA: inhibits phosphorylation and ATP binding
1. Binds to BCR/ABL fusion protein
2. prevents substrate phosphorylation
3. Inhibits signalling so no proliferation or survival

Question 13

What is the use and mode of action of Gefitinib?

Answer 13

Cancer/tumour with high EGFR expression, lung cancer
MOA: inhibits phosphorylation and ATP binding
1. Binds to EGFR-tyrosine kinase domain
2. Stops ATP binding
3. Inhibits downstream signalling cascade, phosphorylation and signalling

Question 14

What is the use and mode of action of Tamoxifen?

Answer 14

Breast cancer
MOA: inhibits oestrogen receptor interaction
1. Competitively binds to oestrogen receptor
2. Inhibits oestrogen regulated gene expression

Question 15

What is the use and mode of action of Dabrafenib and Vemurafenib?

Answer 15

Melanoma
MOA: inhibits MAPK signalling pathway
1. Binds to B-RAF protein
2. Prevents ATP binding and phosphorylation
3. No cell proliferation of B-RAF gene mutation containing tumours

Question 16

What test is needed for Trastuzumab treatment?

Answer 16

HER 2 expression test on tumour biopsy

Question 17

What test is needed for Dabrafenib and Vemurafenib treatment?

Answer 17

B-RAF gene mutation diagnostic test

Question 18

What ways can resistance develop to trastuzumab?

Answer 18

1. HER 2 constitutive activation
2. EGFR compensation- using EGFR family pathway for alternative cell signalling like over expression of TGF alpha
3. Mutation in MAPK/ERK pathway
4. Mutation of HER 2
5. Phosphotase mutations
6. Alternative cell signalling using HER 1
7. Intracellular signalling changes

Question 19

What drugs inhibit pro tumour inflammation?

Answer 19

MAPK inhibitor

Signal inhibitors

Question 20

What drugs promote anti-tumour inflammation by inhibiting immune checkpoints?

Answer 20

Ipilimumab

Nivolumab

Question 21

What are the 2 immune checkpoints targeted in anti-tumour inflammation?

Answer 21

CTLA4

PD1/PDL1

Question 22

What type of drug is Ipilimumab and its MOA?

Answer 22

Anti CTLA4 monoclonal antibody
MOA:
1. Binds to CTLA4 on activated t cells
2. Enhances anti-tumour t cell response

Question 23

What type of drug is Nivolumab and its MOA?

Answer 23

Anti PD1/PDL1 monoclonal antibody 
MOA:
1. Binds to PD1 on dendritic and macrophage cell surface
2. Prevents PD1 and PDL1 interaction  
3. Activates t cell anti-tumour response

Question 24

What drugs are used in chemotherapy treatment?

Answer 24

Intercalating agents
Alkylating agents
Vincrisitine and Vinblastine
Topoisomerase II inhibitor
Metal complexes
Anti metabolites
Taxol

AVITMAT