Natural EGFR inhibitors?

[michele u]

Since i am weakly EGFR positive, does anyone know if there are any supplements or foods that are EGFR inhibitors?

[al from Canada]

Isn't olive oil (oleic acid) an ERB2 inhibiotr?

Al

[michele u]

Does anyone know if taking Flaxseed oil capsules that have 180mg of oleic acid and linoleic acid would do the same thing as taking olive oil? Olive oil is nasty and it has alot of calories in it. Not saying that i won't take it if i have to, but it's expensive too!

[al from Canada]

Hi Michelle,
That's what I give Linda and I cook exclusively with olive oil.

Take care,
Al

The omega three six balance has been reported in trials as impacting on ErbB-2 expression in murine trials. The more I read the more I am convinced at a very amateur level that if you do nothing else at a dietary level it is importatant to try and balance the omega threes and sixes. Fats are fundamental to all life and according to literature on the subject played a large part in evolution or intelligent design which ever you choose.

Flax seed and olive oil are very different, have different constituents and are reported in general terms as being potentially benificial for different reasons. There may be common ground in that they both impact on the lipd pathways, and I would guess have a lot of interactive effects.

Fish oil is a strong recommendation to.

There are lots of posts on this site if you do a searches on omega three, olive oil, fish oil etc.

RB

This is useful link I found that clarifies the differences between EFGR and ErbB -2.

I will keep an eye out for specific links between ErbB -1 (EFGR) and omega three nine olive oil etc.


RB


http://www.iressa.com/iressaHCP/9898_12803_5_1_0.aspx

ABSTRACT

The EGFR family and intracellular signalling
The EGFR is part of a subfamily of four closely related receptors:

* EGFR (ErbB-1)
* Her 2/neu (ErbB-2)
* Her 3 (ErbB-3)
* Her 4 (ErbB-4)

Increased EGFR-mediated signalling can contribute to a cell moving into a state of continuous, uncontrolled cell division; expanding the population of malignant cells and increasing the tumour mass.

The processes by which this occurs begins when the receptors, which are inactive single units or monomers, become activated by the binding of the appropriate ligand.

This causes the receptors to pair together forming a dimer. The dimers may be formed either from two identical receptors, for example the EGF-1 receptor (EGFR) can pair with another EGFR-1 receptor to form a homodimer; or from two non-identical receptors, for example an EGFR can pair with a different receptor such as Her2/neu, forming an asymmetrical homodimer.

The pairing of the receptors activates the tyrosine kinase enzyme located in the intracellular domain of the receptor. This causes both intracellular domains to become transphosphorylated, which, in turn, initiates a cascade of events that eventually results in the signal reaching the nucleus [1] .

The sequence of events that occur when the EGFR becomes activated, leading to the cell moving into a state of continuous, uncontrolled division are as follows:

1. Activated EGFR recruits a number of proteins from the cytoplasm to form a linked complex.
2. Interactions between these proteins leads to the activation of a protein called ras.
3. Activated ras protein initiates a cascade of phosphorylations
4. Phosphorylation cascade activates mitogen activated protein kinase (MAPK)
5. MAP kinase delivers the signal from the cytoplasm to the nucleus
6. Signal reaches nucleus and triggers an accumulation of cyclin D
7. In association with cyclin-dependent kinases (cdks), cyclin D forces the cell to move into the active phase of division [2].


Models of ligand-receptor interactions were traditionally thought of as linear pathways of intracellular signals that link receptor activation to a single cell response. However, we now know that membrane receptor activation results in a number highly complex events in which several pathways are regulated simultaneous [3] .

EGFR is also involved in other processes crucial to tumour progression: apoptosis, angiogenesis and metastasis.


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References

1. Wells A. Molecules in focus EGF receptor. International Journal of Biochemistry and Cell Biology, 1999;31:637-643.
2. Lundberg AS, Weinberg RA Control of the cell cycle and apoptosis. European Journal of Cancer, 1999;35:1886-1894.
3. Brugge JS, McCormick F. Cell regulation intracellular networking. Current Opinion in Cell Biology, 1999;11:173-176.

Here is a site dedicated to EFGR.


RB



http://www.egfr-info.com/Article/501770.aspx

[michele u]

Here's another question. Can one be PTEn positve and EGFR negative? I wonder how many of the women here have been tested for this? Since i'm PTEN positve and EGFR weakly positve, do you think that's why i haven't recurred yet? And does anyone know if Lapatinib is a EGFR inhibitor? Boy, so many things to think about!!

[al from Canada]

Yes, Lapatinib is both an EGFR (HER1) and a HER2 inhibitor. You can be one thing positive and another negative but, some combinations have a propensity for pairing, such as; HER2 and VEGF; HER2 and PTEN; HER2 and PI3K, HER2 and EGFR. Just because your tests don't conform to the "usual' doesn't mean you won't respond to therapy. In fact, even being mildly EGFR + doesn't mean that EGFR inhibitors won't benefit you; because, as I mentioned before, these inhibitors have a way of resensitizing other receptors to targetted therapies.

It's all very complicated stuff and if we new the answers, we might have the disease beat. What is most important is that poeple like yourself keep asking the hard questions so that researchers don't forget to keep looking for the answers.
Take care,
Al

AL.

I posted this in case of interest, on EGFR becoming activated as HER2 is knocked out and cells adapting to a different path.

And a trial with both Herceptin and an EGFR related inhibitor.

A bit beyond me but I think I get the drift, -cancer is complex, multifacted and adaptable.

RB

http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

ABSTRACT

The role of the ErbB family in supporting the malignant phenotype was characterized by stable transfection of a single chain antibody (ScFv5R) against ErbB2 containing a KDEL endoplasmic reticulum retention sequence into GEO human colon carcinoma cells. The antibody traps ErbB2 in the endoplasmic reticulum, thereby down-regulating cell surface ErbB2. The transfected cells showed inactivation of ErbB2 tyrosine phosphorylation and reduced heterodimerization of ErbB2 and ErbB3. This resulted in greater sensitivity to apoptosis induced by growth deprivation and delayed tumorigenicity in vivo. Furthermore, decreased heterodimerization of ErbB2 and ErbB3 led to a reorganization in ErbB function in transfected cells as heterodimerization between epidermal growth factor receptor (EGFR) and ErbB3 increased, whereas ErbB3 activation remained almost the same. Importantly, elimination of ErbB2 signaling resulted in an increase in EGFR expression and activation in transfected cells. Increased EGFR activation contributed to the sustained cell survival in transfected cells.

http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

1: Cancer Res. 2001 Dec 15;61(24):8887-95. Related Articles, Links
Click here to read
Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo.

Moulder SL, Yakes FM, Muthuswamy SK, Bianco R, Simpson JF, Arteaga CL.

Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6307, USA.

Aberrrant signaling by the epidermal growth factor receptor [EGFR (HER1, erbB1)] and/or HER2/neu tyrosine kinases is present in a cohort of breast carcinomas. Because HER2 is constitutively phosphorylated in some breast tumors, we speculated that, in these cancers, transmodulation of HER2 may occur via EGFR signaling. To test this possibility, we examined the effect of EGFR-specific kinase inhibitors against the HER2-overexpressing human breast tumor lines BT-474, SKBR-3, MDA-361, and MDA-453. ZD1839 (Iressa) is an ATP-mimetic that inhibits the purified EGFR and HER2 kinases in vitro with an IC(50) of 0.033 and >3.7 microM, respectively. The specificity of ZD1839 against EGFR was confirmed in Rat1 fibroblasts transfected with EGFR or HER2 chimeric receptors activated by synthetic ligands without the interference of endogenous receptors. Treatment of all breast cancer cell lines (except MDA-453) with 1 microM ZD1839 almost completely eliminated HER2 phosphorylation. In contrast, the incorporation of [gamma-(32)P]ATP in vitro onto HER2 receptors isolated from BT-474 cells was unaffected by 1 microM ZD1839. EGFR is expressed by BT-474, SKBR-3, and MDA-361 but not by MDA-453 cells, suggesting that ZD1839-mediated inhibition of the EGFR kinase explained the inhibition of HER2 phosphorylation in vivo. In SKBR-3 cells, ZD1839 exhibited a greater growth-inhibitory effect than Herceptin, a monoclonal antibody against the HER2 ectodomain. In both SKBR-3 and BT-474 cells, treatment with ZD1839 plus Herceptin induced a greater apoptotic effect than either inhibitor alone. Finally, ZD1839 completely prevented growth of BT-474 xenografts established in nude mice and enhanced the antitumor effect of Herceptin. These data imply that EGFR tyrosine kinase inhibitors will be effective against HER2-overexpressing breast tumor cells that also express EGFR and support their use in combination with HER2 antibodies, such as Herceptin, against mammary carcinomas with high levels of the HER2 proto-oncogene.

PMID: 11751413 [PubMed - indexed for MEDLINE]

[al from Canada]

Thank you, Thank you, Thank you!!! I've been preaching this for I don't know how long. Not that I have all the answers, (any for that matter), but cancer is very sneaky and that's why Linda has asked for an EGFR inhibitor.

Thanks for posting this,
Al

I attended a lecture given a representative of the research department of Genentech and they reported that the combinations of Tarceva/Iressa and Herceptin in clinical trials so far had not shown the synergy they had hoped for(and expected due to the preclinical results). Hopes are higher for the Lapatinib-Herceptin combination. The best article on the matter I have found so far is the following. Please let me know if the link doesn't work (I am a novice at this)

mct.aacrjournals.org/cgi/reprint/3/10/1335

[Karen t]

I have been using extra light olive oil for everything including cakes and pie crusts. This oil has no flavor to speak of so it should work fine for anyone who thinks olive oil is yucky. My question, however, is whether extra light olive oil provides the same level of benefit (or any at all) as compared with regular olive oil?

Check out the posts on olive oil on this site using the search.

There are some previously posted links dealing with the composition of olive oil.

Some brands of processed oils have high omega six content.

Refining may also impact on other benificial elements of the oil, these too were from memory covered in the links.

If you are looking at trying to balance you omea three and sixes this may be a factor you may wish to consider.

Canola has been reported as good for baking is reported as about 22% linoleic (omega six) and has some three 10%. Others question its use.

No easy answers but I would suggest you check out the posts on olive oil and omega threes and sixes.

RB