HER2 Support Group Forums - View Single Post - Entinostat and Lapatinib for HER2-Positive Advanced Disease

donocco · 10-27-2013, 10:36 PM

Elizabeth

I printed some material about Etinostat at work. As you stated it is a Histone de-Acetylase inhibitor. Histones are proteins that block gene expression. Every cell in your body has the same genetic code, but in each area of the body only some genes are active. In the salivary glands the saliva producing genes are active. You have the same saliva genes in the cells lining your eye but these are blocked by histone proteins. If they were not the eye would produce saliva in addition to tears.

There are genes in the cancer cell (I imagine of any type of cancer) that block the cancer cell growth when active. The cancer cells block these anti-growth genes with histone proteins. The body attempts to reactivate these genes by putting acetate molecules in between the histone protein and the DNA making up the anti-growth gene. The acetate under the histone protein "loostens" its grip on the DNA so the anti growth genes are reactivated. The cancer cells fight back by using an Enzyme, Histone De-Acetylase, to remove the acetate and allow the histone protein to " gum up" the antigrowth gene again. The idea of using an HDAC inhibitor like Etinostat is to inhibit this acetate removing enzyme.

The article I read used Etinostat in a dosage of 4mg/meter square only once a week. Etinostat has a half life in the body of about 5 days, so once a week dosing seems to be sufficient. The Etinostat was combined with Cis Retinoic Acid (the anti acne drug Accutane) at a dosage of 1mg /kg. There are retinoic acid genes in the cancer cells that, when acivated, interfere with cancer cell growth but these genes were being blocked. The idea was to use the Etinostat to prevent the cancer cells from reblocking the gene using their Histone deacetylase Enzyme

The side effects of Etinostat at a dosage of 4mg/m2 weekly
were anemia, neutropenia, and hyponatremia (low sodium)

Paul

PS there is a commonly used anti-siezure drug that has strong action as a Histone Deacetylase Inhibitor. The drug is Depakote, generic name Valproic Acid. I imagine it could be used clinically. Certainly there is a lot of experience with the drug.

10-27-2013, 10:36 PM	#2
donocco Senior Member Join Date: Oct 2013 Posts: 474	Re: Entinostat and Lapatinib for HER2-Positive Advanced Disease Elizabeth I printed some material about Etinostat at work. As you stated it is a Histone de-Acetylase inhibitor. Histones are proteins that block gene expression. Every cell in your body has the same genetic code, but in each area of the body only some genes are active. In the salivary glands the saliva producing genes are active. You have the same saliva genes in the cells lining your eye but these are blocked by histone proteins. If they were not the eye would produce saliva in addition to tears. There are genes in the cancer cell (I imagine of any type of cancer) that block the cancer cell growth when active. The cancer cells block these anti-growth genes with histone proteins. The body attempts to reactivate these genes by putting acetate molecules in between the histone protein and the DNA making up the anti-growth gene. The acetate under the histone protein "loostens" its grip on the DNA so the anti growth genes are reactivated. The cancer cells fight back by using an Enzyme, Histone De-Acetylase, to remove the acetate and allow the histone protein to " gum up" the antigrowth gene again. The idea of using an HDAC inhibitor like Etinostat is to inhibit this acetate removing enzyme. The article I read used Etinostat in a dosage of 4mg/meter square only once a week. Etinostat has a half life in the body of about 5 days, so once a week dosing seems to be sufficient. The Etinostat was combined with Cis Retinoic Acid (the anti acne drug Accutane) at a dosage of 1mg /kg. There are retinoic acid genes in the cancer cells that, when acivated, interfere with cancer cell growth but these genes were being blocked. The idea was to use the Etinostat to prevent the cancer cells from reblocking the gene using their Histone deacetylase Enzyme The side effects of Etinostat at a dosage of 4mg/m2 weekly were anemia, neutropenia, and hyponatremia (low sodium) Paul PS there is a commonly used anti-siezure drug that has strong action as a Histone Deacetylase Inhibitor. The drug is Depakote, generic name Valproic Acid. I imagine it could be used clinically. Certainly there is a lot of experience with the drug.