Sunday, December 29, 2013

FARNESYLATION, FRIEND OR FOE

The ascent of KRAS as a therapeutic biomarker in Metastatic Colon cancer has increased the interest in Farnesylation as cellular process because is closely linked with Prenylation, if it is not the same process.
And from wikipedia:

"Proteins that undergo prenylation include Ras, which plays a central role in the development of cancer. This suggests that inhibitors of prenylation enzymes (e.g., farnesyltransferase) may influence tumor growth. In the case of the K- and N-Ras forms of Ras, when cells are treated with FTIs, these forms of Ras can undergo alternate prenylation in the form of geranylgeranylation.[5] Recent work has shown that farnesyltransferase inhibitors (FTIs) also inhibit Rab geranylgeranyltransferase and that the success of such inhibitors in clinical trials may be as much due to effects on Rab prenylation as on Ras prenylation. It should be noted that inhibitors of prenyltransferase enzymes display different specificity for the prenyltransferases, dependent upon the specific compound being utilized." wikipedia

Meaning wild type Ras which benefit from Cetuximab and Panitumumab could be affected if farnesylation is compromised.  Indeed logically, FTI could limit the effect of anti-EGFR because the kind of indrectly "mutate" or disable RAS by making it inattrative to its protein co-activator.  Remember prenylation increases protein-protein interaction.  By the same token, use of statins needs to be carefully reviewed in thiese circumstances since it may impact or block prenylation and there.

Interactions on calcium/ phosphate ratios can impact rate of Alzheimer disease? can we ask if Prenylation has something to do with rates of dementia...a good question to explore fully?

Perturbance of Farnesylation has been linked to Blindness, somewhat contribution to Avastin use in treating some ophthalmic condition (an honest question)?

Lemon derived product are at the source of Farnesol,  is it safe to eat Lemon while with KRAS driven disease?
Many questions to tease our readers!

do remember a gene called PGC1 which interacts
with Farnesoid X Receptor as well as PPARy and the Retinoic X Receptor alpha
PGC1 interect and is down stream from NRF1

All this put Farnesylation at the center of  PI3K pathways in a way!

(IF YOU DON'T REACT TO THIS BLOG, ARE YOU FRIEND OR FOE?)  YOU GOT TO REACT!
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