Signal Transduction Pathway Targeting Extra Reading Flashcards Preview

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Flashcards in Signal Transduction Pathway Targeting Extra Reading Deck (19)
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1
Q

What do Iressa, Glivec and Herceptin have in common?

A

They are all molecular therapeutics targeted to deregulated signal transduction pathways.

Iressa: EGFR tyrosine kinase inhibitor (ATP binding?)
Glivec: Bcr-Abl inhibitor
Herceptin: HER2 extracellular domain.

2
Q

Iressa

A

EGFR tyrosine kinase inhibitor (ATP?)

3
Q

Glivec:

A

Bcr-Abl inhibitor

4
Q

Herceptin

A

HER2 extracellular domain.

5
Q

As most cancers are likely to be driven by the combined effects of several different oncogenes and tumour-suppressor genes (CSC hypothesis etc), it is likely that targeting any one of the deregulated pathways will be sufficient to have what type of therapeutic effect?

A

A cytostatic, rather than cytotoxic effect. Likely to stop any more tumour growth but not to kill the tumour cells.

6
Q

Farnesyl transferase inhibitors are used to treat mutations to which aspect of the Ras -> MAPK kinase pathway?

A

Ras.
Prevent the post-translational modification and membrane localisation of Ras = block the proliferative signal transduction.

7
Q

How do FTIs work?

A

Prevent the post-translational modification and membrane localisation of Ras = block the proliferative signal transduction.

Ras -> MAPK etc.

8
Q

Lonafarib is an example of

A

FTIs.
Prevent the post-translational modification and membrane localisation of Ras = block the proliferative signal transduction.

9
Q

Tipifarnib is an example of

A

Prevent the post-translational modification and membrane localisation of Ras = block the proliferative signal transduction.

10
Q

Signal transduction pathway targeting consists of (4)

A

Farnesyl Transferase Inhibitors (FTIs)
CDKIs
Receptor Tyrosine Kinase Inhibitors (RTKIs)
Protein Kinase C Inhibitors (PKCIs)

11
Q

A CDKI which inhibited CDK4 would have the effects of restoring function to ___

A

p16

12
Q

Receptor Tyrosine Kinase Inhibitors differ from other signal transduction inhibitors such as CDKIs, FTIs how?

A

They target signal transduction at the level of cell membrane receptors, rather than further downstream.

13
Q

Two FTIs in clinical use

A

Tipifarnib
Lonafarib

Prevent the post-translational modification and membrane localisation of Ras = block the proliferative signal transduction.

14
Q

What are the most well known examples of Receptor Tyrosine Kinase Inhibitors?

A

Iressa

Herceptin

15
Q

Glivec inhibits

A

Both PDGF RTK and the tyrosine kinase associated with the Bcr/Abl fusion protein present in patients with chronic myeloid leukaemia (CML).

16
Q

Protein Kinase C (PKC) is one of the

A

Most ubiquitous of intracellular signal transduction targets for inhibition.

At least 12 isoforms exist, and these are intimately involved in cell signals leading to proliferation and differentiation.

17
Q

What is the best example of a PKC inhibitor?

A

Tamoxifen - it is also an oestrogen receptor blocker.

18
Q

Staurosporine is an example of

A

A PKC inhibitor.

19
Q

mTOR inhibitors may have particular utility in tumours which have lost the function of what tumour suppressor gene?

A

PTEN loss leads to activation of P13 kinase pathway.