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Cancer > 8 - Targeted therapy > Flashcards

8 - Targeted therapy Flashcards

1
Q

Targeted therapy

A

Monoclonal antibodies

Small tyrosine kinase inhibitors

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2
Q

What are targeted cancer therapies

A

drugs or other substances that block the growth and spread of cancer by interfering with specific molecules involved in tumour growth and progression

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3
Q

How does tyrosine kinase receptors work

A

GF binds to the binding domain
Activates the MAPK and P13 kinase pathway
Growth, survival and motility

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4
Q

How can biological therapies inhibit cancer

A

Antibody inhibitors of growth factors bind to the growth factor to prevent growth signal
- antibody-drug conjugates target drug to tumour cells

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5
Q

-u

A

human

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6
Q

-zu

A

humanised 95%

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7
Q
  • xi
A

chimeric 65% human

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8
Q

How to inhibit tyrosine kinase receptors

A

Antagonise ligand-receptor signalling

inhibit the dimerisation

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9
Q

EGFR

A

cetuximab

panitumumab

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10
Q

HER2

A

Trastuzumab

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11
Q

HER3

A

Pertuzumab

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12
Q

VEGFR

A

Bavacizumab

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13
Q

How do antibodies access tumour cells

A

Tumour cells have leaky blood vessels
no lymph drainage
antibodies can accumulate

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14
Q

How to MoAbs kill the tumour directly

A

Signalling blocked
Apoptosis induced
Delivery of toxic payload

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15
Q

How do MoAbs kill tumour via immune mediated mechanisms

A

Phagocytosis
Complement dependent cytotoxicity
Antibody dependent cell
Cytotoxicity ASCC

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16
Q

MoA of herceptin (trastuzumab)

A

Attaches to HER2 tyrosine kinase receptor
Inhibits dimerisation so signalling pathways not activated
ADCC - NK cell binds to the MoAb and destroys the tumour cell

17
Q

Targeting the VEGFR

A

Inhibits angiogenesis

18
Q

What is VEGF needed for

A

Formation of nascent blood vessels

Protects endothelial cells from death via activation of PKC pathway and upregulation of anti-apoptotic proteins

19
Q

What occurs when blocking VEGF

A

Inhibits tumour growth and metastasis

Deprives tumours of nutrient providing blood vessels

20
Q

What are small molecule tyrosine kinase inhibitors

A

target oncogene product

e.g getfitinib

21
Q

Which tyrosine kinase domain is associated with drug resistance

A

EGFR

TKI

22
Q

First generation tyrosine kinase inhibitors (reversible)

A

Erlotinib

Gefitinib

23
Q

Second generation EGFR tyrosine kinase inhibitors (irreversible)

A

Afatinib

24
Q

Third gen EGFR tyrosine kinase inhibitors (Mutant-selective)

A

Osimertinib

25
Q

Skin side effects of targeted therapies

A 
Skin rashes (EGFR)
Dry skin 
Itchy skin
Hand foot syndrome (VEGF) 
Changes in hair 
Dry or red eyes
26
Q

other side effects of targeted therapies

A

High BP - VEGF
Slow wound healing and blood clotting - EGFR
Congestive heart failure - HER2
Cardiotoxicity - trastuzamab

Cancer (6 decks)

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