Targeted Cancer Therapy

Question 1

Targeted therapy

Answer 1

Treatment that targets specific molecules driving cancer growth and progression

Question 2

What is adjuvant targeted therapy

Answer 2

Targeted therapy in combo with surgery/chemo/radio

Question 3

Why do targeted therapies have less adverse reactions than other treatments

Answer 3

Less likely to affect molecules involved in other functions and healthy tissues

Question 4

What can biomarkers from molecular profiling be used to assess

Answer 4

Prognosis
Diagnosis
Predict Drug sensitivity/resistance
Predict adverse effects

Question 5

What is used to individualise treatment plans to specific mutations and cancers

Answer 5

Molecular signatures

Question 6

Advantages of treatments targeted to individual patients

Answer 6

Improve diagnosis
Decr side effects
Decr use of ineffective drugs
Incr survival
Incr quality of life
Decr costs

Question 7

Where are the best targets for targeted therapy found

Answer 7

In cancer cells but not in normal cells

Question 8

What happens after a growth factor binds to a tyrosine kinase receptor

Answer 8

Receptor dimerises and kinase activated

Question 9

What is the most important tyrosine kinase receptor involved in cancer

Answer 9

HER2

Question 10

What is the most important oncogenic driver

Answer 10

MAPK pathway

Question 11

How do targeted therapies targeting growth factors or tyrosine kinase receptors treat cancers

Answer 11

Inactivate MAPK and PI3 pathways decreasing cell growth, proliferation, and angiogenesis

Question 12

What are the main targets of targeted therapies

Answer 12

Receptors on plasma membrane
Kinase activity within cells
RAS RAF - kinases

Question 13

2 main types of targeted therapy

Answer 13

Antibodies
Small molecule kinase inhibitors

Question 14

Why do antibodies only have targets on the cell surface membrane

Answer 14

Too big to enter cells

Question 15

Antibodies or small molecule kinase inhibitor more selective

Answer 15

Antibodies

Question 16

How are antibody targeted therapies administered

Answer 16

IV or SC

Question 17

How are small molecule kinase inhibitor targeted therapies administered

Answer 17

Orally

Question 18

What part of tyrosine kinase receptors do small molecule kinase inhibitors bind to

Answer 18

ATP binding site

Question 19

How can antibody targeted therapies disrupt tyrosine kinase receptors

Answer 19

Bind to regions preventing ligand binding, receptor dimerisation, or ATP binding

Question 20

How can monoclonal antibodies kill tumour cells directly

Answer 20

Inhibit ligand binding blocking signalling and inducing apoptosis
Deliver toxic drugs conjugated to the antibody

Question 21

How do monoclonal antibodies kill tumour cells via immune mediated mechanisms

Answer 21

Induce phagocytosis
Complement dependent cytotoxicity
Antibody dependent cell cytotoxicity

Question 22

How can monoclonal antibodies kill tumour cells by vascular or stromal ablation

Answer 22

Antagonise VEGF

Question 23

What type of targeted therapy is cetuximab and what is its MOA

Answer 23

monoclonal antibody
Binds to EFGR kinase receptor preventing dimerisation

Question 24

Kadcycla/trastuzumab emtansine MOA

Answer 24

enters cell bound to antibody -> antibody degraded -> kadcycla causes apoptosis, mitotic arrest, and mitotic catastrophe

Question 25

Do patients become resistant to kadcycla or herceptin first

Answer 25

Herceptin

Question 26

Kinase inhibitor targets

Answer 26

Transcription Receptor tyrosine kinase signalling Proto oncogenes

Question 27

What causes drug resistance to targeted therapies

Answer 27

Mutations to target molecules

Question 28

Why do most HER2 cancer pts eventually become resistant to herceptin

Answer 28

HER2 becomes truncated and the binding site for herceptin is lost but kinase activity is still switched on

Question 29

Which receptor do erlotinib, gefitinib, afatinib, and osimertinib target

Answer 29

EGFR

Question 30

Why is osimertinib used after erlotinib

Answer 30

Pts become resistant to erlotinib

Question 31

Targeted therapy side effects

Answer 31

Acneform Skin rashes EGFR Dry skin Itchy skin Hand foot syndrome VEGF Hair changes Dry or red eyes Red and tender eyelids High blood pressure Slow wound healing and blood clotting

Question 32

Which targeted therapy side effects are specifically associated with EGFR targeting drugs

Answer 32

Skin rashes Slow wound healing and blood clotting

Question 33

Which targeted therapy side effects are specifically associated with VEGF targeting drugs

Answer 33

Hand foot syndrome High blood pressure

Question 34

Why must cardiac function be assessed before and every 3 months during trastumazab use

Answer 34

Cardiomyopathy is side effect

Question 35

Why does trastuzumab cause cardiomyopathies

Answer 35

Inhibiting HER2 damages cardiomyocytes

Question 36

What type of heart failure is caused by trastuzumab

Answer 36

Congestive