Molecular targeted Therapy

Question 1

Alkylating agents

Answer 1

Cyclophosphamide
Melphalan
Chlorambucil

Question 2

Antimetabolites

Answer 2

Methotrexate

Question 3

Plant alkaloids

Answer 3

Taxanes

Vinca alkaloids

Question 4

Hormones + antagonists

Answer 4

Anti-oestrogens

Anti-androgens

Question 5

Targeted therapy

Answer 5

Monoclonal antibodies

Small TKIs

Question 6

Breast cancer genetics

Answer 6

13-20% overexpress HER2

- HR2 Gene amplification

Question 7

Breast cancer treatment

Answer 7

Trastuzumab

Lapantanib

Question 8

Colorectal cancer genetics

Answer 8

35-50% overexpress EGFR
Polysomy or EGFR gene amplification + wild-type RAS only
Metastatic cancer in liver

Question 9

Colorectal cancer

Answer 9

Combination of Cetuximab with Oxaliplatin-containing chemo

Question 10

Lung cancer genetics

Answer 10

15% EGFR-positive- somatic mutations
some in TK domain
usually late diagnosis, poor prognosis

Question 11

Lung cancer treatment

Answer 11

Afatinib (EGFR/HER2)
Erlotinib
Gefitinib
Bevacizumab

Question 12

Melanoma genetics

Answer 12

> 50% with unresectable or metastatic melanoma have a mutation in the BRAF
20% patients don’t initially respond

Question 13

Melanoma treatment

Answer 13

Vemurafenib
Dabrafenib
Trametinib

Question 14

Antibody inhibitors of growth receptors

Answer 14

Bind to growth factor receptors and prevent growth signals

Question 15

Antibody-drug conjugates

Answer 15

Antibody targets drug to tumour cells

Question 16

TKI of growth receptors

Answer 16

Bind to growth receptors + prevent growth signals

Question 17

Alemtuzumab (CLL)

Answer 17

Naked antibody

Activate immune system

Question 18

Pembrolizumab (melanoma)

Answer 18

Naked antibody

Target immune system checkpoints

Question 19

Herceptin (breast cancer)

Answer 19

Naked antibody

Inhibiting activity of antigen + prevent growth

Question 20

MOA monoclonal antibodies

Answer 20

Kill tumour directly
Kill tumour via an immune-mediated mechanism
Vascular or stromal ablation

Question 21

VEGF

Answer 21

Required for formation of nascent blood vessels
Protects endothelial cells from death via activation of PKC pathways + upregulation of anti-apoptotic proteins such as Bcl-2
Activity modified by TK receptors- VEGFR1 + VEGFR2
Most upregulated genes in cancer- survival of tumour cells

Question 22

Targetting VEGFR

Answer 22

Antibody target
Angiogenesis inhibited
Deprives tumours of nutrient-providing blood vessels

Question 23

TKI inhibitors targets

Answer 23

Inhibit intracellular TK enzymes to inhibit ATP binding
Target oncogene product
Inhibit signalling at key steps
Safer than chemo

Question 24

Side effects of targeted therapy

Answer 24

Rash- EGFR
Hand foot syndrome- VEGF
High BP- VEGF
Slow wound healing/clotting- EGFR
Congestive HF- HER2

Question 25

-tinib

Answer 25

TKI

Question 26

-zomib

Answer 26

proteasome inhibitor

Question 27

-ciclib

Answer 27

cyclin-dependent kinase inhibitor

Question 28

-parib

Answer 28

poly ADP-ribose polymerase inhibitor

Question 29

EGFR Family TKRIs | Extracellular + Intracellular AAs

Answer 29

Extra- 630 | Intra- 560

Question 30

target EGFR

Answer 30

Cetuximab

Question 31

target HER2

Answer 31

Trastuxumab

Question 32

target HER2/3

Answer 32

Pertuzumab

Question 33

target VEGFR

Answer 33

Bevacizumab

Question 34

Trastuzumab

Answer 34

Bind to domain IV on HER2 | Suppresses ligand-independent HER2 signalling

Question 35

Pertuzumab

Answer 35

Binds to domain II on HER2 | Supresses ligand-dependent HER2 signalling

Question 36

Fab in monoclonal antibody

Answer 36

selective monoclonal antibody targets tumour specific or tumour associated antigens

Question 37

Fc in monoclonal antibody

Answer 37

Has potent cytotoxic payload

Question 38

Tyrosine Kinases nomenclature

Answer 38

-tinib

Question 39

Mutations in TK domain of EGFR in lung cancer

Answer 39

exon 18,19,20,21

Question 40

Drug resistance

Answer 40

70% women don't respond/resistant to trastuzumab | Most develop resistacne to TKI

Question 41

Trastuzamab

Answer 41

Cardiotoxicity | Decline in LV cardiac function